# Patent

## Title
Bifidobacterium longum

## Abstract

The multiple embodiments described herein comprise the genome of a probiotic Bifidobacterium longum bifidobacteria strain and genes encoded by the genome. Various novel Bifidobacterium longum are described.

## Background
CROSS-REFERENCES TO RELATED APPLICATIONS
The present application claims the benefit of U.S. Provisional Application No. 61/113,513 filed Nov. 11, 2008, and U.S. Provisional Application No. 61/149,980 filed Feb. 4, 2009 the complete contents of both of which are incorporated herein by reference.


FIELD OF THE INVENTION
The invention relates to the genome of a probiotic bifidobacteria strain and genes encoded by the genome. Bifidobacteria are one of several predominant culturable bacteria present in human colonic microflora.
BACKGROUND OF THE INVENTION
Bifidobacteria are considered to be probiotics as they are living organisms which exert healthy effects beyond basic nutrition when ingested in sufficient numbers. A high level of ingested bifidobacteria must reach their site of action in order to exert a probiotic effect. A minimum level of approximately 106-107 viable bifidobacteria per gram intestinal contents has been suggested (Bouhnik, Y., Lait 1993). There are reports in the literature which show that in vivo studies completed in adults and in infants indicate that some strains of bifidobacteria are capable of surviving passage through the gastrointestinal tract. Significant differences have been observed between the abilities of different bifidobacteria strains to tolerate acid and bile salts, indicating that survival is an important criterion for the selection of potential probiotic strains.
Ingestion of bifidobacteria can improve gastrointestinal transit and may prevent or assist in the treatment of illnesses which may be caused by deficient or compromised microflora such as gastrointestinal tract (GIT) infections, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)—Crohn's disease and ulcerative colitis, food allergies, antibiotic-induced diarrhoea, cardiovascular disease, and certain cancers (e.g. colorectal cancer).
Because of their perceived health-promoting activities, bifidobacteria have in recent years enjoyed an increased amount of scientific scrutiny, which included the full genomic sequencing of a number of strains (reviewed by Liu et al., 2005). These genomic sequences will provide the genetic platforms that allow the study of the molecular mechanisms by which these micro organisms interact with their human host and elicit their probiotic function.
SUMMARY OF THE INVENTION
The invention provides an isolated and purified Bifidobacterium longum strain, excluding Bifidobacterium longum strain 35624 (NCIMB 41003), wherein the strain:

    
    
        a) expresses an exopolysaccharide; and
        b) comprises at least two nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto.
    
    


A Bifidobacterium longum strain according to the invention may include any 2 or more such as BI00778, BI00793; BI00778,BI00794; BI00778,BI00795 or any three or more such as BI00793,BI00794,BI00798; BI00794,BI00795,BI00796; BI00796,BI00797,BI00798 or any four or more such as BI00778,BI00779,BI00780,BI00794; BI00778,BI00779,BI00785,BI00786; BI00790,BI00791,BI00794,BI00798 or any five or more such as BI00783,BI00786,BI00790,BI00794,BI00798; BI00780,BI00782,BI00785,BI00786,BI00790; BI00778,BI00779,BI00787,BI00789,BI00798 or any six or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00794; BI00782,BI00784,BI00785,BI00788,BI00792,BI00797; BI00781,BI00782,BI00783,BI00791,BI00796,BI00797 or any seven or more such as BI00779,BI00783,BI00784,BI00787,BI00791,BI00792,BI00797; BI00780,BI00789,BI00790,BI00793,BI00794,BI00797,BI00798; BI00783,BI00784,BI00786,BI00788,BI00789,BI00793,BI00796 or any eight or more such as BI00779,BI00782,BI00783,BI00784,BI00785,BI00794,BI00797,BI00798; BI00780,BI00787,BI00788,BI00789,BI00790,BI00793,BI00794,BI00795; BI00783,BI00784,BI00785,BI00786,BI00787,BI00793,BI00795,BI00798 or any nine or more such as BI00778,BI00780,BI00782,BI00784,BI00785,BI00787,BI00793,BI00795,BI00796; BI00779,BI00781,BI00782,BI00784,BI00786,BI00787,BI00793,BI00795,BI00797; BI00782,BI00783,BI00785,BI00786,BI00787,BI00789,BI00792,BI00796,BI00797 or any ten or more such as BI00778,BI00781,BI00784,BI00785,BI00786,BI00789,BI00790,BI00792,BI00793,BI00798; BI00779,BI00781,BI00784,BI00786,BI00787,BI00788,BI00791,BI00794,BI00795,BI00796; BI00782,BI00784,BI00785,BI00786,BI00790,BI00792,BI00794,BI00796,BI00797,BI00798 or any eleven or more such as BI00778,BI00781,BI00785,BI00787,BI00788,BI00790,BI00791,BI00792,BI00794,BI00795,BI00798; BI00779,BI00782,BI00785,BI00786,BI00789,BI00790,BI00793,BI00794,BI00795,BI00796, BI00797; BI00781,BI00783,BI00785,BI00787,BI00788,BI00789,BI00790,BI00793,BI00794,BI00795,BI00796 or any twelve or more such as BI00778,BI00781,BI00782,BI00783,BI00784,BI00785,BI00790,BI00791,BI00792,BI00795,BI00796,BI00797; BI00779,BI00785,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00794,BI00796,BI00797,BI00798; BI00786,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00793,BI00795,BI00796,BI00797,BI00798 or any thirteen or more such as BI00778,BI00779,BI00780,BI00782,BI00784,BI00789,BI00790,BI00791,BI00792,BI00793, BI00794,BI00795,BI00798; BI00778,BI00781,BI00782,BI00783,BI00786,BI00787,BI00789,BI00790,BI00791,BI00792,BI00795,BI00796,BI00798; BI00780,BI00781,BI00782,BI00783,BI00785,BI00786,BI00788,BI00790,BI00791,BI00792,BI00793,BI00797,BI00798 or any fourteen or more such as BI00778,BI00779,BI00780,BI00782,BI00783,BI00784,BI00785,BI00787,BI00789,BI00791,BI00793,BI00794,BI00795,BI00797; BI00778,BI00780,BI00781,BI00782,BI00784,BI00785,BI00786,BI00788,BI00789,BI00792,BI00793 ,BI00794,BI00796,BI00797; BI00779,BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00787,BI00790,BI00791, BI00794,BI00796,BI00797,BI00798 or any fifteen or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789,BI00790,BI00792,BI00798; BI00778,BI00780,BI00781,BI00782,BI00785,BI00787,BI00788,BI00789,BI00790,BI00791,BI00793,BI00794,BI00795,BI00796,BI00798; BI00780,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00789,BI00790,BI00791,BI00793,BI00795,BI00796,BI00797,BI00798 or any sixteen or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00784,BI00785,BI00787,BI00789,BI00790,BI00791,BI00792,BI00793,BI00795,BI00797,BI00798; BI00778,BI00779,BI00781,BI00783,BI00784,BI00785,BI00787,BI00788,BI00789,BI00790, B00791,BI00792,BI00794,BI00795,BI00797,BI00798; BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00787,BI00788,BI00789,BI00790,BI00792,BI00793,BI00795,BI00796,BI00797,BI00798 or any seventeen or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00784,BI00785,BI00787,BI00788,BI00789,BI00790,BI00793,BI00794,BI00795,BI00796,BI00797,BI00798; BI00778,BI00780,BI00781,BI00782,BI00783,BI00785,BI00786,BI00787,BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00797; BI00779,BI00780,BI00782,BI00783,BI00784,BI00785,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00797,BI00798 or any eighteen or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00787,BI00788,BI00789,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00798; BI00778,BI00779,BI00781,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789,BI00790,BI00792,BI00794,BI00795,BI00796,BI00797,BI00798; BI00779,BI00781,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789, BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00797 or any nineteen or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00794,BI00795,BI00796,BI00797; BI00778,BI00779,BI00780,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788, BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00797; BI00779,BI00780,BI00781,BI00782,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00797,BI00798 or any twenty or more such as BI00778,BI00779,BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00797,BI00798; BI00778,BI00779,BI00780,BI00781,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00797,BI00798; BI00778,BI00779,BI00780,BI00782,BI00783,BI00784,BI00785,BI00786,BI00787,BI00788,BI00789,BI00790,BI00791,BI00792,BI00793,BI00794,BI00795,BI00796,BI00797,BI00798 or all twenty one of the nucleic acid sequences selected from the group comprising SEQ ID No. 93 to SEQ ID No. 113 or sequences homologous thereto.
The strain may comprise at least three nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least four nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least five nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least six nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least seven nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least eight nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least nine nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least ten nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least twelve nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least three nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least thirteen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least fourteen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least fifteen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least sixteen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least seventeen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least eighteen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least nineteen nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least twenty nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise all twenty one nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto.
The strain may not comprise the nucleic acid sequence of SEQ ID No. 112.
The strain may comprise at least one nucleic acid sequence selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto.
The strain may comprise at least two nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least three nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least four nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least five nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least six nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least seven nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least eight nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least nine nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least ten nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least eleven nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least twelve nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least thirteen nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least fourteen nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least fifteen nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least sixteen nucleic acid sequence selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least seventeen nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise at least eigteens nucleic acid sequence selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise all ninteen nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto
The strain may comprise a single nucleic acid sequence selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least sequence homology thereto. The strain may comprise a nucleic acid sequence of SEQ ID No. 132 or a nucleic acid sequence with at least sequence homology thereto.
The strain may comprise two nucleic acid sequences selected from the group comprising SEQ ID No. 114 to SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto. The strain may comprise the nucleic acid sequences of SEQ ID No. 131 and SEQ ID No. 132 or nucleic acid sequences with at least 85% sequence homology thereto.
The invention also provides an isolated and purified Bifidobacterium longum strain wherein the strain:

    
    
        a) expresses an exopolysaccharide; and
        b) comprises at least two nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto; and
        c) comprises a nucleic acid sequence of SEQ ID No. 132 or a nucleic acid sequence with at least 85% sequence homology thereto; and/or
        d) comprises a nucleic acid sequence of SEQ ID No. 131 or a nucleic acid sequence with at least 85% sequence homology thereto.
    
    


In one embodiment, 1×107 CFU/ml of the strain may induce an [IL10]: [IL12] ratio of at least 10 in a peripheral blood mononuclear cell (PMBC) co-incubation assay. The strain may be in the form of a bacterial broth. The strain may be in the form of a freeze-dried powder.
The invention further provides an isolated and purified Bifidobacterium longum strain wherein the strain:

    
    
        a) expresses an exopolysaccharide; and
        b) comprises at least two nucleic acid sequences selected from the group comprising SEQ ID NO. 93 to SEQ ID No. 113 or nucleic acid sequences with at least 85% sequence homology thereto; and
        c) comprises a nucleic acid sequence of SEQ ID No. 132 or a nucleic acid sequence with at least 85% sequence homology thereto; and/or a nucleic acid sequence of SEQ ID No. 131 or a nucleic acid sequence with at least 85% sequence homology thereto; and
        d) induces an [IL10]: [IL12] ratio of at least 10 in a peripheral blood mononuclear cell (PMBC) co-incubation assay at a concentration of 1×107 CFU/ml bacteria.
    
    


The invention also provides an isolated strain of Bifidobacterium longum BL1207 (PTA-9608).
The invention further provides an isolated strain of Bifidobacterium longum AH121A (NCIMB 41675).
The invention further still provides an isolated strain of Bifidobacterium longum AH1714 (NCIMB 41676).
The isolated strain may be in the form of viable cells. The isolated strain may be in the form of non-viable cells.
The invention also provides a formulation comprising an isolated strain of Bifidobacterium longum as described herein. The formulation may comprise an ingestable carrier. The ingestable carrier may be a pharmaceutically acceptable carrier such as a capsule, tablet or powder. The ingestable carrier may be a food product such as acidified milk, yoghurt, frozen yoghurt, milk powder, milk concentrate, cheese spreads, dressings or beverages. The formulation may comprise a strain that is present at more than 106 cfu per gram of ingestable carrier.
The invention further provides a composition comprising an isolated strain of Bifidobacterium longum as described herein and a pharmaceutically acceptable carrier.
The invention also provides for the use of a Bifidobacterium longum strain as described herein as a probiotic strain.
The invention also provides a method for identifying an exopolysaccharide expressing Bifidobacterium longum strain comprising the steps of:

    
    
        a) obtaining a sample comprising bacteria;
        b) extracting nucleic acid from the sample;
        c) amplifying the extracted nucleic acid in the presence of at least two primers derived from a nucleic acid sequence selected from the group comprising: SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 10 to SEQ ID No. 12, SEQ ID No. 93 to SEQ ID No. 132 or a nucleic acid sequence with at least 85% sequence homology thereto;
        d) identifying a bacterial strain that expresses an exopolysaccharide.
    
    


The primer may comprise at least 10 consecutive bases from a nucleic acid sequence selected from the group comprising: SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 10 to SEQ ID No. 12 and SEQ ID No. 93 to SEQ ID No. 132.
The primer may comprise a nucleic acid sequence selected from the group comprising: SEQ ID No. 10 to SEQ ID No. 12, SEQ ID No. 13 to SEQ ID No. 92 or a nucleic acid sequence with at least 85% sequence homology thereto.
The step of identifying a bacterial strain that expresses an exopolysaccharide may comprise growing the bacterial strain on a Congo red agar plate.
The sample is a mammalian sample. The sample may be a human derived sample. The sample may be a fecal sample.
The invention also provides for a Bifidobacterium longum strain identified by described herein. The Bifidobacterium longum strain may be in the form of viable cells. The Bifidobacterium longum strain may be in the form of non-viable cells.
The invention further provides for a formulation comprising a Bifidobacterium longum strain as described herein. The formulation may comprise an ingestable carrier. The ingestable carrier may be a pharmaceutically acceptable carrier such as a capsule, tablet or powder. The ingestable carrier may be a food product such as acidified milk, yoghurt, frozen yoghurt, milk powder, milk concentrate, cheese spreads, dressings or beverages. The strain may be present at more than 106 cfu per gram of ingestable carrier in the formulation.
The invention also provides a composition comprising a Bifidobacterium longum strain as described herein and a pharmaceutically acceptable carrier.
In one embodiment of the invention there is a method for identifying exopolysaccharide secreting bacterial strains comprising the steps of:

    
    
        obtaining a sample comprising bacteria;
        extracting DNA from the sample;
        amplifying the extracted DNA in the presence of at least one DNA primer derived from the DNA sequence of SEQ ID No. 2 and/or SEQ ID No. 3; and
        identifying a bacterial strain that expresses an exopolysaccharide.
    
    


The extracted DNA may be amplified by real time PCR. The DNA may be amplified in the presence of at least one primer of the nucleic acid sequence of SEQ ID No. 10, SEQ ID No. 11 or SEQ ID No. 12.
The sample may be a human derived sample such as a fecal sample.
In another embodiment, the invention also provides for a bacterial strain identified by the method described herein.
In another embodiment, the invention further provides for the use of a bacterial strain identified by the method described herein as a probiotic bacteria.
In yet another embodiment, the invention also provides a formulation comprising a bacterial strain identified by the method described herein.
In another embodiment, the invention further provides a composition comprising a bacterial strain identified by the method described herein and a pharmaceutically acceptable carrier.
In another embodiment, the invention also provides an isolated bifidobacterial longum strain BL1207 (PTA-9608).
In yet another embodiment, the invention further provides a formulation comprising an isolated bifidobacterial longum strain BL1207 (PTA-9608).
In another embodiment, the invention also provides a composition comprising an isolated bifidobacterial longum strain BL1207 (PTA-9608) and a pharmaceutically acceptable carrier.
In another embodiment, the invention further provides a DNA array/chip comprising at least one polynucleotide derived from the nucleic acid sequence of SEQ ID NO. 1, SEQ ID No. 2, or SEQ ID No. 3.
In one embodiment, the invention also provides a computer readable medium comprising a nucleic acid sequence of SEQ ID NO. 1, SEQ ID No. 2, or SEQ ID No. 3 or parts thereof.
A Bifidobacterium longum strain in accordance with an embodiment of the invention may express or produce EPS at a yield of between about 10 mg/L to about 1000 mg/L of bacterial culture.
There are a number of strains of Bifidobacteria which are already deposited under the Budapest Treaty. These include the strain deposited at the NCIMB under the number 41003, the genome of which is presented herein. As this is a known strain, this strain is specifically disclaimed for the claims to the strains per se. In so far as the following strains may fall within the scope of the patent claims at the relevant date(s), the following claims are also disclaimed: ATCC BAA-999, CNCM I-1227, CNCM I-1228, CNCM I-2168, CNCM I-2170, CNCM I-2618, CNCM I-3446, CNCM I-3853, CNCM I-3854, CNCM I-3855, NCIMB 41290, NCIMB 41291, NCIMB 41382, NCIMB 41387, NTCC 2705.



BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be more clearly understood from the following description thereof given by way of example only with reference to the accompanying drawings in which;
FIG. 1 is a Genome atlas of Bifidobacterium longum biotype infantis UCC 35624. The numbers on the genome (1, 1000001, 200001) refer to base pair position. 1 refers to the adenine nucleotide of the ATG start codon of the gene encoding the predicted replication protein. The outer circle (two strands, black and white) refers to the gene density within the chromosome. The second circle (middle circle—black) refers to the GC content and the innermost circle refers to the GC skew;
FIG. 2 is a bar chart showing the induction profile of IL-1beta in PBMCs by Bifidobacterium longum infantis strain UCC35624 (B624), Bifidobacterium longum strain 1207 (BL1207), Bifidobacterium longum strain 15707 (BL15707), Bifidobacterium lactis (BL-07) and Bifidobacterium breve strain 8807 [UCC2003] (breve);
FIG. 3 is a bar chart showing the induction profile of IL-12p70 in PBMCs by Bifidobacterium longum infantis strain UCC35624 (B624), Bifidobacterium longum strain 1207 (BL1207), Bifidobacterium longum strain 15707 (BL15707), Bifidobacterium lactis (BL-07) and Bifidobacterium breve strain 8807 [UCC2003] (breve);
FIG. 4 is a bar chart showing the induction profile of IL-10 in PBMCs by Bifidobacterium longum infantis strain UCC35624 (B624), Bifidobacterium longum strain 1207 (BL1207), Bifidobacterium longum strain 15707 (BL15707), Bifidobacterium lactis (BL-07) and Bifidobacterium breve strain 8807 [UCC2003] (breve);
FIG. 5 is a bar chart showing the induction profile of TNF-alpha in PBMCs by Bifidobacterium longum infantis strain UCC35624 (B624), Bifidobacterium longum strain 1207 (BL1207), Bifidobacterium longum strain 15707 (BL15707), Bifidobacterium lactis (BL-07) and Bifidobacterium breve strain 8807 [UCC2003] (breve).
FIG. 6 is a photograph of B. longum 35624 grown on a Congo Red Agar plate;
FIG. 7 is a photograph of B. longum AH121A grown on a Congo Red Agar plate;
FIG. 8 is a photograph of B. longum AH1714 grown on a Congo Red Agar plate;
FIG. 9 is a photograph of B. longum AH0119 grown on a Congo Red Agar plate;
FIG. 10 is a photograph of B. breve UCC2003 grown on a Congo Red Agar plate;
FIG. 11 is a photograph of L. Rhamnosus AH308 grown on a Congo Red Agar plate;
FIG. 12 is a photograph of L. salivarius UCC1 grown on a Congo Red Agar plate; and
FIG. 13 is a bar chart illustrating the IL-10:IL-12p70 ratio for PBMCs stimulated with Bifidobacterium longum infantis strain 35624 (Bifidobacterium 35624), Bifidobacterium longum strain 1714 (Bifidobacterium 1714), Bifidobacterium longum strain 1207 (Bifidobacterium 1207), Bifidobacterium longum strain 12IA (Bifidobacterium 121A), Bifidobacterium longum strain 0119 (Bifidobacterium 0119), Bifidobacterium longum strain 15707 (Bifidobacterium 15707), Bifidobacterium breve strain 8807 (Bifidobacterium UCC2003), Lactobacillus rhamnosus and Lactobacillus salivarius strain UCC1.



DETAILED DESCRIPTION OF THE INVENTION
Disclosed herein is an isolated polynucleotide of SEQ ID No. 1. The polynucleotide of SEQ ID No. 1 encodes a strain of Bifidobacterium. The Bifidobacterium encoded by the isolated polynucleotide sequence has a number of unique genes. The unique genes encoded by the polynucleotide have a unique order in the sequence of SEQ ID No. 1. As used herein, the term “unique genes”, mean genes that are not found in the currently available sequences of Bifodobacterium. As used herein, the term “unique order”, means that the position/sequence of the genes in the polynucleotide is not found in the currently available sequences of Bifodobacterium. The unique genes present in the isolated polynucleotide may be interspersed with nucleic acid residues that code for other (known) genes or stretches of non-coding sequence but the overall order/sequence of the unique genes in the isolated polynucleotide is in itself unique compared to the order of genes found in the currently available sequences of Bifodobacterium. 
The polynucleotide was isolated from a strain of the bacterial species Bifidobacterium longum biotype infantis with the strain designation UCC 35624. A deposit of Bifidobacterium longum biotype infantis strain UCC 35624 was made at the National Collections of Industrial and Marine Bacteria Limited (NCIMB) Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland, UK on Jan. 13, 1999 and accorded the accession number NCIMB 41003.
A deposit of Bifidobacteria infantis strain BL1207 was made at the American Type Culture Collection (ATTC) 10801 University Boulevard, Manassas, Va. 20110-2209, USA on Nov. 14, 2008 and accorded the accession number PTA-9608.
A deposit of Bifidobacterium longum strain AH121A was made at the National Collections of Industrial and Marine Bacteria Limited (NCIMB) Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland, UK on Nov. 5, 2009 and accorded the accession number NCIMB 41675.
A deposit of Bifidobacterium longum strain AH1714 was made at the National Collections of Industrial and Marine Bacteria Limited (NCIMB) Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland, UK on Nov. 5, 2009 and accorded the accession number NCIMB 41676.
Given the size of the isolated polynucleotide it would not be uncommon for a point mutation or some other form of mutation to be present in the sequence. As such we encompass variants of SEQ ID No. 1 in the disclosure. As used herein, the term “variants”, means strains of Bifidobacteria that have a sequence identity of at least 99.5% or more with SEQ ID No. 1.
SEQ ID No. 1 contains a large number of open reading frames which represent the predicted genes. We have identified 1,836 protein coding regions or genes within this polynucleotide. As such, our disclosure encompasses fragments of the polynucleotide of SEQ ID No. 1. The fragments may correspond to portions of the polynucleotide sequence that encode one or more proteins. Alternatively, the fragments may correspond to portions of the polynucleotide sequence that specify part of a gene or genes for example the fragment may correspond to a portion of the polynucleotide sequence that spans a part of two or more genes.
The sequence of SEQ ID No. 1 is a DNA polynucleotide sequence, our disclosure encompasses sequences that are complementary to the DNA sequence for example complementary DNA (cDNA) or RNA sequences including messenger RNA (mRNA) and transfer RNA (tRNA) or protein sequences such as amino acid sequences encoded by the polynucleotide sequence.
The polynucleotide of SEQ ID No.1 and complementary sequences thereof may take many forms for example an isolated polynucleotide sequence; an isolated protein sequence; a biologically pure culture of a Bifidobacterial strain comprising the nucleic acid of SEQ ID NO. 1; a plasmid comprising the polynucleotide of SEQ ID No. 1; and the like. All of these forms of the sequence of SEQ ID No. 1 are encompassed in this disclosure.
As used herein, the term “expresses an exopolysaccharide”, may be interpreted to mean that a bacterial strain contains a DNA sequence encoding an exopolysaccharide for example a DNA sequence that encodes at least one gene from SEQ ID No. 2 and/or at least one gene from SEQ ID No. 3 or a functional fragment or variant thereof.
As used herein, the term “sequence homology” encompasses sequence homology at a nucleic acid and/or an amino acid (protein) level. Sequence homology is indicated as the overall percentage of identity across the nucleic acid and/or amino acid sequence. The sequence homology may be determined using standard techniques known to those skilled in the art. For example sequence homology may be determined using the on-line homology algorithm “BLAST” program, publicly available at. A sequence may have at least 85% or at least 86% or at least 87% or at least 88% or at least 89% or at lest 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% sequence homology with the nucleic acid sequences described herein or the amino acid (protein) encoded thereby.
The present invention is based on the whole genome sequence of Bifidobacterium longum biotype infantis UCC 35624. The genome sequence is listed in SEQ ID No. 1 of the attached sequence listing and comprises 2,264374 base pairs. Analysis of the genome sequence identified 1,836 genes having the open reading frames as set out in Table 1 below.







TABLE 1







Open reading frames of the genome of UCC 35624.











GeneID
Start
End
Strand
Description














BI00001
1667321
1667608
−
CRISPR-associated protein Cas2


BI00002
1667697
1668593
−
CRISPR-associated protein Cas1


BI00002a
1668725
1669423
−
CRISPR-associated protein Cas4


BI00003
1669465
1670313
−
CRISPR-associated protein, TM1801 family


BI00005
1670320
1672275
−
CRISPR-associated protein, CT1133 family


BI00006
1672281
1672982
−
CRISPR-associated protein, CT1134 family


BI00007
1672992
1675427
−
hypothetical CRISPR-associated helicase Cas3


BI00008
1676109
1676426
−
COG3464: Transposase and inactivated






derivatives


BI00009
1677053
1680283
−
isoleucyl-tRNA synthetase


BI00010
1680955
1682163
+
aminotransferase, class I, putative


BI00011
1682280
1683785
−
galactoside symporter


BI00012
1684111
1687299
+
beta-galactosidase, putative


BI00013
1687365
1688372
−
sugar-binding transcriptional regulator, LacI






family, putative


BI00014
1688522
1689889
−
Putative antibiotic resistance protein (membrane






protein)


BI00015
1690007
1690906
−
hypothetical pfkB family carbohydrate kinase


BI00016
1690909
1692111
−
alcohol dehydrogenase, iron-containing


BI00017
1692111
1692794
−
hypothetical haloacid dehalogenase-like hydrolase


BI00018
1692921
1693901
−
inosine-uridine preferring nucleoside hydrolase


BI00019
1693960
1694913
−
hypothetical pfkB family carbohydrate kinase


BI00020
1694909
1695553
−
hypothetical N-(5′phosphoribosyl)anthranilate






isomerase


BI00021
1695603
1696415
−
ABC transporter, ATP-binding protein


BI00022
1696415
1697242
−
conserved hypothetical protein


BI00023
1697246
1698055
−
hypothetical Cobalt transport protein


BI00024
1698062
1698712
−
conserved hypothetical protein


BI00025
1698969
1700846
+
transcriptional regulator, LacI






family/carbohydrate kinase, PfkB family protein


BI00026
1700977
1702989
−
ABC transporter, ATP-binding/permease protein


BI00027
1702989
1704944
−
ABC transporter, ATP-binding protein


BI00028
1704944
1705402
−
transcriptional regulator, MarR family, putative


BI00029
1705699
1706610
−
COG1472: Beta-glucosidase-related glycosidases


BI00030
1706029
1706937
+
COG1309: Transcriptional regulator


BI00031
1707015
1708373
−
unnamed protein product


BI00032
1708509
1710902
−
xylosidase/arabinosidase [imported]


BI00033
1710937
1711287
−
hypothetical protein


BI00034
1711383
1712762
−
glutamate--cysteine ligase, putative


BI00035
1712905
1718037
+
conserved domain protein


BI00036
1718044
1718883
+
hypothetical protein


BI00037
1719052
1724187
−
BadF/BadG/BcrA/BcrD ATPase family family


BI00038
1724418
1725143
−
anaerobic ribonucleoside-triphosphate reductase






activating protein


BI00039
1725294
1727699
−
anaerobic ribonucleoside-triphosphate reductase


BI00040
1728167
1729534
+
exodeoxyribonuclease VII, large subunit


BI00041
1729587
1729886
+
exodeoxyribonuclease VII, small subunit


BI00042
1730013
1730534
+
NADP(H) oxidoreductase CC0205 [imported]


BI00043
1730676
1732529
−
long-chain-fatty-acid--CoA ligase, putative


BI00044
1732662
1732787
−
COG1970: Large-conductance mechanosensitive






channel


BI00045
1732765
1733166
−
hypothetical Large-conductance mechanosensitive






channel, MscL


BI00046
1733337
1733762
−
UNKNOWN PROTEIN, putative


BI00047
1733887
1734102
−
COG0454: Histone acetyltransferase HPA2 and






related acetyltransferases


BI00048
1734587
1735696
+
hypothetical transmembrane protein with






unknown function


BI00049
1735718
1736683
−
exopolyphosphatase, putative


BI00050
1736864
1737967
−
aminotransferase, class I


BI00051
1738178
1739230
+
oxidoreductase, Gfo/Idh/MocA family, putative


BI00052
1739267
1739779
−
patch repair protein [imported]


BI00053
1739931
1740377
+
acetyltransferase, GNAT family


BI00054
1740356
1740841
−
conserved hypothetical protein


BI00055
1741026
1745207
−
helicase, Snf2 family


BI00056
1745285
1746367
+
conserved hypothetical protein


BI00057
1746358
1746504
−
hypothetical protein


BI00058
1746604
1747620
+
tetrahydrodipicolinate N-succinyltransferase






(dapD)


BI00059
1747840
1749129
−
citrate synthase I


BI00060
1749406
1750242
−
methionine aminopeptidase, type I


BI00061
1750378
1751355
−
membrane protein, putative


BI00062
1751532
1753703
+
belongs to peptidase family M13


BI00063
1753792
1754526
−
single-stranded DNA-binding protein (ssb)






subfamily


BI00064
1754805
1756616
−
prolyl-tRNA synthetase


BI00065
1757008
1757361
+
hypothetical protein


BI00066
1757392
1758561
−
pflA


BI00067
1758551
1760338
−
Protein of unknown function family


BI00068
1760391
1761806
−
TPR domain protein


BI00069
1761858
1762505
−
oligoribonuclease


BI00070
1762676
1764259
−
inosine-5′-monophosphate dehydrogenase


BI00071
1764282
1765562
−
undecaprenyl-phosphate alpha-N-






acetylglucosaminyltransferase


BI00072
1765562
1766233
−
Sua5/YciO/YrdC/YwlC family protein


BI00073
1766408
1767082
+
maltose O-acetyltransferase


BI00074
1767220
1767921
−
branched-chain amino acid ABC transporter,






ATP-binding protein


BI00075
1767924
1768781
−
branched chain amino acid ABC transporter,






ATP-binding protein


BI00076
1768781
1769854
−
branched-chain amino acid ABC transporter,






permease protein


BI00077
1769874
1770797
−
branched-chain amino acid ABC transporter,






permease protein


BI00078
1771042
1772226
−
branched-chain amino acid ABC transporter,






amino acid-binding protein, putative


BI00079
1772502
1773407
−
N-methylase PapM


BI00080
1773473
1774492
−
peptide chain release factor 1


BI00003g
1774715
1774924
−
ribosomal protein L31


BI00081
1775256
1776482
−
transcription regulator ROK family VC2007






[imported], putative


BI00082
1776702
1778219
+
xylulokinase


BI00083
1778416
1778760
+
lipoprotein, putative


BI00084
1778773
1779114
+
hypothetical protein


BI00085
1779393
1779737
−
possible sugar permease


BI00086
1779656
1780930
−
transposase, Mutator family


BI00087
1781199
1782545
−
xylose isomerase


BI00088
1782842
1783072
+
drug resistance transporter, EmrB/QacA






subfamily


BI00089
1783095
1783409
+
drug resistance transporter, EmrB/QacA






subfamily


BI00090
1783425
1784222
−
conserved hypothetical protein


BI00091
1785149
1785661
−
polypeptide deformylase


BI00092
1785576
1786421
−
oxidoreductase, aldo/keto reductase family






superfamily


BI00093
1786497
1786673
−
COG0477: Permeases of the major facilitator






superfamily


BI00094
1786761
1787264
−
hypothetical COG0477: Permeases of the major






facilitator superfamily


BI00095
1787291
1787791
−
possible MarR-type transcriptional regulator


BI00011g
1787998
1788333
−
hypothetical protein Blon021361


BI00096
1788358
1789572
−
sugar ABC transporter, permease protein


BI00097
1789575
1791125
−
sugar ABC transporter, ATP-binding protein


BI00098
1791229
1792383
−
sugar ABC transporter, periplasmic sugar-binding






protein


BI00099
1792462
1792608
−
hypothetical protein


BI00100
1792854
1793801
+
probable repressor protein in (NagC/XylR) family


BI00101
1793842
1794705
+
sugar ABC transporter, ATP-binding protein,






putative


BI00102
1794736
1795683
−
glucokinase, putative


BI00103
1796537
1798192
+
ATP binding protein of ABC transporter


BI00104
1798507
1799409
+
acyl-CoA thioesterase II


BI00105
1799511
1800035
−
hypothetical membrane protein with unknown






function


BI00106
1800213
1801622
−
dihydroneopterin aldolase


BI00107
1801736
1802608
−
dihydropteroate synthase


BI00108
1802699
1803295
−
GTP cyclohydrolase I


BI00109
1803391
1805478
−
cell division protein FtsH


BI00110
1805478
1806038
−
hypoxanthine phosphoribosyltransferase


BI00111
1806028
1807191
−
COG0037: Predicted ATPase of the PP-loop






superfamily implicated


BI00112
1807285
1808772
−
D-alanyl-D-alanine carboxypeptidase/D-alanyl-D-






alanine-endopeptidase


BI00113
1808798
1810468
−
hypothetical transmembrane protein with






unknown function


BI00114
1810468
1811421
−
ATP-binding protein of ABC transporter system


BI00115
1811519
1812739
−
glycosyl transferase domain protein, putative


BI00116
1812742
1814496
−
hypothetical integral membrane protein in






upfo118


BI00117
1814587
1815252
+
probable glycosyltransferase


BI00118
1815481
1816629
−
alcohol dehydrogenase, iron-containing


BI00119
1817069
1818370
+
cyclopropane-fatty-acyl-phospholipid synthase


BI00120
1818383
1819687
+
hypothetical COG0477: Permeases of the major






facilitator superfamily


BI00121
1820205
1821215
−
UDP-glucose 4-epimerase


BI00122
1821585
1822400
+
methyltransferase, putative


BI00123
1822698
1823195
−
hypothetical protein


BI00124
1823244
1823708
−
Orf2


BI00125
1823795
1824079
+
hypothetical Helix-turn-helix


BI00126
1824492
1824788
−
hypothetical protein


BI00127
1825086
1826453
−
gp22


BI00128
1827148
1827699
−
hypothetical protein


BI00170t
1827699
1828901
−
hypothetical Phage integrase family


BI00129
1829429
1830229
+
azlC protein, putative


BI00130
1830229
1830558
+
branched-chain amino acid permease


BI00131
1830743
1831258
−
phosphotyrosine protein phosphatase, putative


BI00132
1831385
1832044
−
dihydrofolate reductase


BI00133
1832157
1832936
−
thymidylate synthase


BI00134
1833154
1833564
+
conserved hypothetical protein


BI00135
1833629
1834663
−
demannu, putative


BI00136
1834835
1835572
−
P60 extracellular protein, invasion associated






protein Iap


BI00137
1835733
1836476
−
NLP/P60 family domain protein


BI00138
1836692
1837645
−
N-acetylmuramoyl-L-alanine amidase domain






protein


BI00139
1838255
1839178
+
phosphoserine aminotransferase, putative


BI00140
1839305
1839562
+
conserved hypothetical protein


BI00141
1839693
1840874
−
sensor histidine kinase, putative


BI00142
1841128
1841745
+
phosphate transport system regulatory protein






PhoU, putative


BI00143
1842110
1842847
−
phosphoglycerate mutase


BI00144
1842910
1843872
−
1,4-dihydroxy-2-naphthoate octaprenyltransferase


BI00145
1843937
1845412
−
lysyl-tRNA synthetase


BI00146
1846534
1847304
+
AraJ-like protein probably involved in transport






of arabinose polymers


BI00147
1847394
1849754
+
TPR Domain domain protein


BI00148
1849833
1850462
+
conserved hypothetical protein


BI00149
1850618
1852216
−
hypothetical membrane protein possibly involved






in transport


BI00150
1852325
1853029
−
conserved hypothetical protein


BI00151
1853062
1854903
−
conserved hypothetical protein


BI00152
1854930
1856174
+
possible histidine kinase sensor of two component






system


BI00153
1856174
1856866
+
transcription regulator, LuxR family NMB1250






[imported]


BI00154
1856920
1857939
−
UDP-glucose 4-epimerase


BI00155
1858012
1859556
−
galactose-1-phosphate uridylyltransferase


BI00156
1859606
1860682
−
putative desulfatase possibly for mucin


BI00157
1860713
1862965
−
conserved hypothetical protein


BI00158
1863426
1864382
−
sugar ABC transporter, permease protein


BI00159
1864382
1865278
−
sugar ABC transporter, permease protein, putative


BI00160
1865546
1866859
−
solute binding protein of ABC transporter for






sugars


BI00161
1867217
1867369
−
hypothetical protein


BI00162
1867867
1868856
−
seryl-tRNA synthetase


BI00163
1869384
1870562
+
Diacylglycerol kinase catalytic domain






(presumed) protein


BI00164
1870573
1871409
−
transcription antiterminator, BglG family, putative


BI00165
1871430
1873829
−
PTS system component, putative


BI00166
1874293
1875843
+
major facilitator family transporter CC0814






[imported], putative


BI00167
1875934
1877607
+
phosphoglucomutase, alpha-D-glucose phosphate-






specific


BI00222t
1878343
1879437
−
conserved hypothetical protein


BI00168
1879668
1880087
+
conserved hypothetical protein


BI00169
1880224
1881837
+
oxidoreductase, pyridine nucleotide-disulfide,






class I


BI00170
1882002
1882151
−
hypothetical protein


BI00171
1882305
1883360
+
RNase H


BI00172
1883494
1884189
+
ribose 5-phosphate isomerase


BI00173
1884629
1885258
−
conserved hypothetical protein


BI00174
1885386
1886921
+
DNA repair protein RadA


BI00175
1886942
1888063
−
riboflavin biosynthesis protein RibF


BI00176
1888164
1889324
−
tRNA pseudouridine synthase B


BI00177
1889329
1889799
−
ribosome-binding factor A


BI00178
1889953
1892799
−
translation initiation factor IF-2


BI00179
1893150
1894214
−
N utilization substance protein A


BI00180
1894422
1895147
+
lipoprotein, putative


BI00181
1895194
1896234
−
transcriptional regulator, LacI family, putative


BI00182
1896528
1896629
−
hypothetical protein


BI00183
1896770
1897798
−
hypothetical


BI00184
1897936
1898568
−
alpha-L-arabinosidase


BI00185
1899147
1899917
−
Transglutaminase-like superfamily domain






protein


BI00186
1900154
1902331
−
Domain of unknown function (DUF404) family


BI00187
1902473
1902586
−
hypothetical protein


BI00188
1902727
1903515
+
tRNA pseudouridine synthase A


BI00189
1903603
1904142
−
ribosomal protein L17


BI00190
1904245
1905237
−
RNA polymerases L/13 to 16 kDa subunit


BI00191
1905321
1905716
−
ribosomal protein S11


BI00192
1905807
1906181
−
ribosomal protein S13p/S18e


BI00193
1906333
1906443
−
ribosomal protein L36


BI00194
1906470
1906685
−
translation initiation factor IF-1


BI00195
1906865
1907422
−
adenylate kinase


BI00196
1907595
1908722
−
preprotein translocase, SecY subunit


BI00197
1909207
1909656
−
ribosomal protein L15


BI00198
1909662
1909844
−
ribosomal protein L30


BI00199
1909853
1910581
−
ribosomal protein S5


BI00200
1910581
1910991
−
ribosomal protein L18


BI00201
1910954
1911490
−
ribosomal protein L6


BI00202
1911511
1911906
−
ribosomal protein S8


BI00203
1911999
1912181
−
ribosomal protein S14p/S29e


BI00204
1912186
1912755
−
ribosomal protein L5 VC2584 [imported]


BI00205
1912755
1913087
−
ribosomal protein L24


BI00206
1913092
1913457
−
ribosomal protein L14


BI00207
1913555
1913812
−
ribosomal protein S17


BI00208
1913818
1914066
−
ribosomal protein L29


BI00209
1914069
1914485
−
ribosomal protein L16


BI00210
1914495
1915295
−
ribosomal protein S3


BI00211
1915301
1915657
−
ribosomal protein L22


BI00212
1915677
1915952
−
ribosomal protein S19


BI00213
1915971
1916798
−
ribosomal protein L2


BI00214
1916838
1917131
−
ribosomal protein L23


BI00215
1917140
1917793
−
ribosomal protein L4/L1 family


BI00216
1917803
1918441
−
ribosomal protein L3


BI00217
1918461
1918766
−
ribosomal protein S10


BI00218
1919023
1920027
+
membrane protein, putative


BI00219
1920366
1923092
−
Unknown


BI00220
1923607
1924797
+
probable repressor in the Rok (NagC/XylR)






family


BI00221
1924797
1927334
+
glycogen operon protein GlgX


BI00222
1927431
1927919
−
ribosomal protein S9


BI00223
1927945
1928391
−
ribosomal protein L13


BI00224
1928792
1930954
−
4-alpha-glucanotransferase


BI00225
1931125
1931931
−
hypothetical Leucine rich repeat variant


BI00226
1931876
1932514
−
conserved hypothetical protein TIGR00257


BI00227
1932579
1933592
−
possible 2-hydroxyacid dehydrogenase


BI00228
1933669
1935009
−
capA protein, putative


BI00229
1935547
1936608
−
COG0697: Permeases of the drug/metabolite






transporter (DMT) superfamily


BI00230
1936648
1937991
+
DNA-damage-inducible protein P


BI00231
1938024
1939256
−
aminotransferase, putative


BI00232
1939374
1939691
−
fdxC


BI00233
1939755
1941278
−
possible cationic amino acid transporter


BI00234
1941433
1942398
−
UDP-N-acetylenolpyruvoylglucosamine reductase


BI00235
1942930
1943094
−
ribosomal protein L33


BI00236
1943529
1944245
+
possible cystathionine gamma lyase


BI00237
1944924
1945214
−
chaperonin, 10 kDa


BI00238
1945390
1946604
−
conserved hypothetical protein


BI00239
1946895
1947557
−
rimJ


BI00240
1947644
1948360
+
5-formyltetrahydrofolate cyclo-ligase-related






protein


BI00241
1948527
1948709
+
conserved hypothetical protein


BI00242
1948950
1949516
+
conserved hypothetical protein


BI00243
1949617
1949814
−
hypothetical protein Blon021580


BI00244
1949820
1953440
−
conserved hypothetical protein


BI00245
1953452
1954999
−
conserved hypothetical protein


BI00246
1955200
1955577
−
ribosomal protein L7/L12


BI00247
1955689
1956207
−
ribosomal protein L10


BI00248
1956479
1957222
−
conserved hypothetical protein


BI00249
1957561
1958952
+
Unknown


BI00250
1959385
1962123
−
polyribonucleotide nucleotidyltransferase


BI00251
1962444
1962710
−
ribosomal protein S15


BI00252
1962882
1963562
−
conserved hypothetical protein


BI00253
1963721
1963951
−
hypothetical protein


BI00254
1964091
1966964
−
possible extracellular exo-xylanase


BI00255
1967190
1969712
−
endo-1,4-beta-xylanase D


BI00256
1970329
1971432
+
IS30 family, transposase [imported]


BI00257
1971591
1972274
−
conserved hypothetical protein


BI00334t
1972174
1972389
+
conserved hypothetical protein


BI00258
1972411
1973094
−
hypothetical protein Blon021028


BI00259
1973553
1974914
−
possible cell surface protein


BI00260
1974994
1977351
−
von Willebrand factor type A domain protein


BI00261
1978150
1978326
−
hypothetical protein Blon021305


BI00262
1978353
1978820
−
phosphopantethiene protein transferase


BI00263
1979459
1988974
−
MaoC like domain protein


BI00264
1989016
1990635
−
propionyl-CoA carboxylase, beta chain


BI00265
1990631
1992514
−
accA3


BI00266
1993105
1993701
+
bioY protein


BI00267
1993739
1994710
−
biotin--acetyl-CoA-carboxylase ligase


BI00268
1994853
1996895
+
membrane protein, putative


BI00269
1996904
1997731
+
conserved hypothetical protein


BI00270
1997829
1998524
−
transcriptional regulator, putative


BI00350t
1998629
1999459
−
hypothetical transcriptional regulator, IclR family


BI00271
2011598
2011726
−
hypothetical protein


BI00272
2011797
2012486
−
ribosomal protein L1


BI00273
2012505
2012933
−
ribosomal protein L11


BI00274
2013199
2014089
−
transcription termination/antitermination factor






NusG


BI00275
2014122
2014346
−
preprotein translocase SecE subunit


BI00276
2014593
2015795
−
aspartate aminotransferase [imported]


BI00277
2015889
2016986
−
glutamate 5-kinase


BI00278
2017023
2018711
−
GTP-binding protein


BI00279
2018783
2019028
−
ribosomal protein L27


BI00280
2019054
2019359
−
ribosomal protein L21


BI00281
2019502
2022534
−
hypothetical ribonuclease, Rne/Rng family


BI00282
2022850
2024121
−
succinyl-diaminopimelate desuccinylase


BI00283
2024159
2025100
+
transporter, putative


BI00284
2025282
2026727
−
permease, putative domain protein


BI00285
2026727
2027818
−
ABC transporter, ATP-binding protein


BI00286
2027996
2029441
−
Maf-like protein


BI00287
2029581
2030690
−
homoserine kinase


BI00288
2030800
2032113
−
homoserine dehydrogenase


BI00289
2032276
2033865
−
diaminopimelate decarboxylase


BI00290
2033871
2035541
−
arginyl-tRNA synthetase


BI00291
2035944
2036606
+
possible TetR-type transcriptional regulator


BI00292
2036606
2037880
+
permease, putative


BI00293
2037742
2038899
+
transcription regulator LysR family VC1588






[imported], putative


BI00294
2038996
2040246
+
probable aminotransferase


BI00295
2040298
2041521
−
UDP-N-acetylglucosamine 1-






carboxyvinyltransferase


BI00296
2041869
2043212
+
NADH oxidase


BI00297
2043424
2044548
−
dihydroorotate dehydrogenase family protein,






putative


BI00298
2044591
2046468
−
CAAX amino terminal protease family protein






family


BI00299
2046594
2047283
−
3-isopropylmalate dehydratase small subunit


BI00300
2047369
2048769
−
3-isopropylmalate dehydratase, large subunit


BI00301
2049087
2049860
+
transcriptional regulator, IclR family


BI00302
2050021
2051391
−
Ser/Thr protein phosphatase family


BI00303
2051896
2054130
+
polyphosphate kinase


BI00304
2054291
2055487
+
mutT1


BI00305
2055480
2056298
+
hypothetical protein Blon021115


BI00306
2056564
2057871
−
conserved hypothetical protein


BI00307
2057963
2058121
−
hypothetical protein


BI00308
2058175
2058813
+
uracil phosphoribosyltransferase


BI00309
2058864
2059340
+
conserved hypothetical protein TIGR00246


BI00310
2059542
2060648
−
possible phosphodiesterase


BI00311
2060677
2061747
−
glutamyl-tRNA synthetase domain protein


BI00312
2061933
2064599
−
ATP-dependent Clp protease, ATP-binding






subunit ClpB


BI00313
2064821
2066371
−
histidine ammonia-lyase


BI00314
2066617
2067489
+
transcriptional regulator, IclR family, putative


BI00315
2067489
2067662
+
conserved hypothetical protein


BI00316
2067741
2068559
−
possible 2-hydroxyhepta-2,4-diene-1,7-dioate






isomerase in the fumarylacetoacetate hydrolase






family


BI00317
2068665
2069873
−
hypothetical membrane protein with unknown






function


BI00318
2070097
2071272
−
UDP-galactopyranose mutase


BI00319
2071426
2072670
+
dTDP-glucose 4,6-dehydratase


BI00320
2072827
2074311
+
conserved hypothetical protein


BI00321
2074367
2075068
+
conserved hypothetical protein


BI00423t
2075382
2075687
+
putative transposase


BI00322
2075763
2076530
−
IS1533, OrfB


BI00323
2076530
2077987
−
transposase (25) BH3998 [imported], putative


BI00324
2078280
2078996
−
glycosyltransferase, putative


BI00325
2079313
2079666
−
sialic acid-specific 9-O-acetylesterase


BI00326
2080049
2081173
+
hypothetical Acyltransferase family


BI00327
2081181
2082893
−
hypothetical membrane protein with unknown






function


BI00328
2082902
2085811
−
hypothetical Glycosyl transferase family 8


BI00329
2085935
2087170
−
hypothetical glycosyl transferase, group 2 family






protein


BI00330
2087259
2088509
−
polysaccharide ABC transporter, ATP-binding






protein


BI00331
2088515
2089351
−
polysaccharide ABC transporter, permease






protein, putative


BI00332
2089580
2091367
+
hypothetical Glycosyl transferase family 8


BI00333
2091457
2092698
−
UDP-glucose 6-dehydrogenase


BI00334
2092974
2093636
+
hypothetical NAD dependent






epimerase/dehydratase family


BI00335
2093654
2094844
−
membrane protein, putative


BI00336
2094847
2097099
−
conserved hypothetical protein


BI00337
2097441
2098844
+
hypothetical membrane protein with unknown






function


BI00338
2098844
2099962
+
possible ATP binding protein of ABC transporter


BI00339
2100089
2100790
+
HDIG domain protein


BI00340
2100871
2101728
−
conserved hypothetical protein


BI00341
2101825
2104335
−
Kup system potassium uptake protein [imported]


BI00342
2104481
2105188
−
hydrolase, TatD family


BI00343
2105717
2106784
+
Fic protein family family


BI00344
2106816
2108621
−
ABC transporter, ATP-binding/permease protein


BI00345
2108635
2110542
−
ABC transporter, ATP-binding/permease protein


BI00346
2110935
2111099
−
hypothetical protein


BI00347
2111297
2112703
−
possible alpha-galactosidase


BI00348
2113077
2114231
+
transcriptional regulator, LacI family, putative


BI00349
2114409
2115356
−
probable AraC/XylS-type transcriptional regulator


BI00350
2115401
2117626
−
conserved hypothetical protein


BI00351
2117851
2119374
+
aminopeptidase C


BI00352
2119555
2120628
+
conserved hypothetical protein


BI00353
2121673
2123403
−
methionyl-tRNA synthetase


BI00354
2123873
2124496
+
conserved hypothetical protein


BI00466t
2124496
2124864
+
conserved hypothetical protein


BI00355
2124897
2125922
−
conserved hypothetical protein TIGR00096


BI00356
2126487
2127902
−
possible symporter


BI00357
2127864
2129027
+
conserved hypothetical protein


BI00358
2129186
2131012
−
ABC transporter, ATP-binding/permease protein


BI00359
2131231
2133099
−
ABC transporter, ATP-binding/permease protein


BI00360
2133289
2133684
−
transcriptional regulator, MarR family, putative


BI00475t
2134267
2134506
+
DNA-damage-inducible protein of Escherichia






coli


BI00361
2135008
2138841
−
LPXTG-motif cell wall anchor domain protein


BI00362
2139056
2139151
−
hypothetical protein


BI00363
2139209
2143594
−
secreted protein


BI00364
2143901
2145394
−
ATP-dependent DNA helicase recG


BI00365
2145737
2147257
−
amino acid permease


BI00366
2147448
2151185
−
permease, putative


BI00367
2151199
2151897
−
ABC transporter, ATP-binding protein


BI00368
2152041
2152607
+
probable TetR-like transcriptional regulator


BI00369
2152832
2154310
+
aromatic amino acid transport protein AroP


BI00370
2154575
2155774
+
putative invertase/transposase


BI00371
2155961
2160952
−
hypothetical Glycosyl hydrolases family 43


BI00372
2161359
2164649
−
hypothetical


BI00373
2164997
2168173
−
possible arabinosidase


BI00374
2168529
2169131
−
conserved hypothetical protein


BI00375
2169340
2170179
−
sugar ABC transporter, permease protein, putative


BI00376
2170182
2171033
−
sugar ABC transporter, permease protein, putative


BI00377
2171416
2172429
+
transcription regulator, LacI family [imported],






putative


BI00378
2172690
2174015
−
possible solute binding protein of ABC






transporter


BI00379
2174424
2175134
−
phosphoglycerate mutase family protein


BI00380
2175226
2175600
+
hypothetical COG0531: Amino acid transporters


BI00381
2175612
2176550
+
hypothetical nitroreductase family protein


BI00382
2176846
2179572
+
phage infectio, putative


BI00383
2179572
2181908
+
phage infection protein, putative


BI00384
2188511
2189263
+
regulatory protein, SIR2 family


BI00385
2189415
2190791
−
threonine dehydratase


BI00386
2190928
2192745
−
glucan 1,6-alpha-glucosidase


BI00387
2192872
2194731
−
hypothetical Raffinose synthase or seed






imbibition protein Sip1


BI00388
2194766
2196433
−
alpha-amylase family protein


BI00389
2196537
2197358
−
hypothetical abc transporter permease protein






yurm. {bacillus


BI00390
2197364
2198383
−
hypothetical Binding-protein-dependent transport






systems inner membrane component


BI00391
2198408
2199730
−
hypothetical Bacterial extracellular solute-binding






protein


BI00392
2199980
2201095
−
hypothetical protein Efae022644


BI00393
2201159
2202484
−
hypothetical Bacterial extracellular solute-binding






protein


BI00394
2202692
2203717
+
transcription regulator, LacI family [imported],






putative


BI00395
2203838
2204854
+
transcription regulator, LacI family [imported],






putative


BI00396
2204919
2205782
−
sugar ABC transporter, permease protein


BI00397
2205804
2206730
−
sugar ABC transporter, permease protein


BI00398
2206755
2208041
−
sugar ABC transporter, sugar-binding protein,






putative


BI00399
2208215
2209420
+
transcription regulator ROK family VC2007






[imported], putative


BI00400
2209591
2211894
−
alpha-galactosidase


BI00401
2212017
2212445
−
hypothetical Cytidine and deoxycytidylate






deaminase zinc-binding region


BI00402
2212589
2214658
+
Na+/H+ antiporter


BI00403
2214858
2215613
−
serine esterase, putative


BI00404
2215613
2215714
−
hypothetical protein


BI00405
2215735
2216592
−
conserved hypothetical protein


BI00406
2216949
2217527
+
deoxycytidine triphosphate deaminase


BI00407
2217593
2219320
+
cell wall surface anchor family protein, putative


BI00408
2219543
2222527
−
calcium E1-E2-type ATPase


BI00409
2222713
2223447
−
protein probably involved in xylan degradation,






possible xylan esterase


BI00410
2223622
2225049
−
hypothetical major facilitator superfamily protein


BI00411
2225005
2225994
+
RNA methyltransferase, TrmH family, group 3


BI00412
2226107
2227516
−
conserved hypothetical protein


BI00413
2227740
2228864
−
ATP binding protein of ABC transporter for






sugars


BI00414
2229226
2230419
−
glycosyl transferase domain protein


BI00415
2230486
2231475
−
Ribonucleotide reductase, beta subunit


BI00416
2231704
2233896
−
ribonucleoside-diphosphate reductase, alpha






subunit


BI00417
2234015
2234470
−
nrdI protein


BI00418
2234470
2234733
−
COG0695: Glutaredoxin and related proteins


BI00419
2235324
2235767
−
hypothetical Helix-turn-helix


BI00420
2235958
2236635
−
conserved hypothetical protein


BI00421
2236828
2237592
+
ion transporter


BI00422
2237788
2238891
+
conserved hypothetical protein


BI00423
2239035
2239349
−
beta-glucosidase-related glycosidase


BI00424
2239828
2241951
+
widely conserved protein with eukaryotic protein






kinase domain


BI00425
2242132
2243106
+
conserved hypothetical protein


BI00426
2243627
2245111
+
conserved hypothetical protein


BI00427
2245147
2246067
+
dimethyladenosine transferase


BI00428
2246067
2247014
+
kinase, GHMP family, group 2


BI00429
2246860
2247690
+
hypothetical protein BL0655


BI00430
2247781
2249193
−
pcnA


BI00431
2249280
2250569
+
NUDIX domain protein


BI00432
2250569
2252836
+
cell wall surface anchor family protein, putative


BI00433
2252836
2254560
+
conserved hypothetical membrane protein in






MviN family


BI00434
2254646
2256706
+
conserved hypothetical protein


BI00435
2256829
2257845
+
thioredoxin reductase


BI00436
2258158
2259516
−
chromosome partitioning protein ParB


BI00437
2259519
2260487
−
Soj family protein


BI00438
2260741
2261403
−
methyltransferase GidB


BI00439
2261558
2262088
−
R3H domain protein


BI00440
2262215
2263219
−
inner membrane protein, 60 kDa VC0004






[imported]


BI00143g
2263219
2263533
−
conserved hypothetical protein TIGR00278


BI00576t
2263533
2264063
−
ribonuclease P protein component


BI00441
2263925
2264056
−
ribosomal protein L34


BI00442
1
1500
+
chromosomal replication initiator protein DnaA


BI00443
2239
3360
+
DNA polymerase III, beta subunit


BI00444
3442
4626
+
recF protein


BI00445
4626
5093
+
conserved hypothetical protein


BI00446
5229
7364
+
DNA gyrase, B subunit


BI00447
7534
10083
+
DNA gyrase, A subunit


BI00448
10156
10719
+
conserved hypothetical protein


BI00449
11406
12116
+
hypothetical protein


BI00450
12179
13699
+
hypothetical Pectinesterase


BI00451
14103
15446
−
NADP-specific glutamate dehydrogenase


BI00452
15768
16199
−
AsnC-type transcriptional regulator


BI00453
16405
17736
+
aspartate aminotransferase


BI00454
17757
18746
−
hypothetical protein Blon021073


BI00455
19007
19600
+
hypothetical protein BL0627


BI00456
19770
20462
+
hypothetical protein Blon021075


BI00457
20579
20821
+
Putative acrab operon repressor transcription






regulator protein


BI00599t
21403
21735
−
IS1557, transposase, putative


BI00146g
21834
22397
−
conserved hypothetical protein


BI00458
22130
23497
−
hypothetical COG1167: Transcriptional regulators






containing a DNA-binding HTH domain and an






aminotransferase domain (MocR family) and their






eukaryotic orthologs


BI00459
24132
25454
+
aminotransferase, class III superfamily


BI00460
25495
26397
+
Zinc metalloprotease


BI00461
26414
26509
−
hypothetical protein


BI00462
26487
26849
+
COG3265: Gluconate kinase


BI00463
27114
28424
−
conserved hypothetical protein


BI00464
28662
29138
−
Dps family protein, putative


BI00465
29238
30608
−
CBS domain protein, putative


BI00466
30841
31521
−
Prokaryotic-type carbonic anhydrases


BI00467
31727
32287
+
alkyl hydrogen peroxide reductase


BI00468
32458
34371
+
thioredoxin reductase


BI00469
34494
35963
−
oxalate: formate antiporter


BI00470
35948
36094
+
hypothetical protein


BI00471
36333
37328
+
LacI-type transcriptional regulator


BI00472
37558
40308
−
phosphoenolpyruvate carboxylase


BI00473
40594
42471
+
membrane protein, putative


BI00474
42737
44344
+
possible sodium/proline symporter


BI00475
44680
45663
−
narrowly conserved hypothetical protein


BI00476
45917
47533
+
conserved hypothetical protein


BI00477
47717
48805
−
tryptophanyl-tRNA synthetase


BI00478
49056
49325
+
hypothetical protein


BI00479
49437
49967
−
conserved hypothetical protein


BI00480
49986
52505
+
glycogen phosphorylase


BI00481
52725
52940
−
hypothetical protein BL0595


BI00482
53195
53887
+
Rhomboid family protein


BI00483
54562
55029
−
conserved hypothetical protein


BI00484
55119
55907
+
conserved hypothetical protein


BI00485
55907
57142
+
hypothetical transmembrane protein with






unknown function


BI00486
57196
57837
+
pabA


BI00487
58067
60136
−
serine/threonine protein kinase


BI00488
60136
60942
−
serine/threonine protein kinase


BI00489
61083
62546
−
pbpA


BI00490
62546
64204
−
Unknown, putative


BI00491
64204
65895
−
possible phosphoprotein phosphatase


BI00492
65903
66430
−
FHA-domain-containing proteins


BI00493
66463
67161
−
FHA domain protein


BI00494
67349
69790
−
dipeptidyl peptidase IV, putative


BI00495
69951
70997
+
lysophospholipase L2, putative


BI00496
71080
72228
+
von Willebrand factor type A domain protein


BI00497
72231
72947
+
conserved hypothetical protein


BI00498
72947
73348
+
hypothetical protein Blon021556


BI00654t
73348
73497
+
hypothetical protein Blon021556


BI00499
73873
74724
+
tellurite resistance protein


BI00500
75108
75608
+
heat shock protein, Hsp20 family


BI00501
75938
76891
+
Probable transmembrane protein


BI00502
77065
77520
−
conserved hypothetical protein


BI00503
77753
79132
+
COG0627: Predicted esterase


BI00504
79132
81702
+
COG2898: Uncharacterized BCR


BI00505
82241
83212
+
peptide methionine sulfoxide reductase


BI00506
83218
83304
+
hypothetical protein BL0567


BI00668t
83341
83496
+
COG0463: Glycosyltransferases involved in cell






wall biogenesis


BI00507
83506
86709
−
helicase-related protein


BI00509
86785
87195
−
mutator MutT protein, putative


BI00510
87337
88587
+
hypothetical Domain of unknown function


BI00511
88678
89139
+
acetyltransferase, GNAT family family


BI00512
89226
90080
−
hypothetical


BI00513
90187
90420
−
hypothetical protein


BI00514
90480
90842
+
conserved hypothetical protein


BI00515
91329
92639
−
queuine tRNA-ribosyltransferase


BI00516
93056
95065
+
heat shock protein HtrA


BI00517
95480
97636
+
cation-transporting ATPase, E1-E2 family


BI00684t
97816
98862
+
transcriptional regulator, LacI family


BI00518
98874
99131
−
hypothetical mttA/Hcf106 family


BI00519
99136
100215
−
Sec-independent protein translocase TatC


BI00687t
100215
100730
−
hypothetical twin-arginine translocation protein,






TatA/E family


BI00520
101182
103581
+
hypothetical Tat (twin-arginine translocation)






pathway signal sequence


BI00521
103674
106151
+
hypothetical


BI00522
106547
107707
−
conserved hypothetical protein


BI00523
107911
109359
+
ferredoxin/ferredoxin--NADP reductase, putative


BI00524
109452
110450
+
heat shock protein HtpX


BI00525
110667
111731
−
fructose-bisphosphate aldolase, class II


BI00526
111947
113230
+
adenylosuccinate synthetase


BI00527
113524
114837
+
chloride channel


BI00528
115027
116094
+
CrcB-like protein family


BI00700t
116097
116489
+
protein with similarity to CrcB


BI00529
116581
116691
+
hypothetical protein


BI00530
116767
117849
+
sugar-binding transcriptional regulator, LacI






family, putative


BI00531
118274
119842
+
Kup system potassium uptake protein [imported]


BI00532
120262
121806
+
alpha-L-arabinofuranosidase


BI00533
121981
123012
+
transcription regulator, LacI family [imported],






putative


BI00534
123104
124012
−
glycosyl hydrolase, family 31


BI00535
124149
124370
−
IS861, transposase OrfB


BI00711t
124604
125803
+
probable integrase/recombinase


BI00712t
125878
126765
+
probable integrase/recombinase


BI00536
126765
127817
+
integrase/recombinase XerC, probable [imported],






putative


BI00537
127910
128956
−
IS3 family transposase


BI00538
129291
130814
+
sucrose phosphorylase


BI00539
131035
132669
+
hypothetical transmembrane protein with






unknown function


BI00540
132736
133776
+
sugar-binding transcriptional regulator, LacI






family, putative


BI00541
134407
135771
+
major facilitator family transporter


BI00542
135971
137020
+
ketol-acid reductoisomerase


BI00543
137452
138501
+
ketol-acid reductoisomerase


BI00544
138689
140500
−
alpha-amylase family protein


BI00545
140663
141694
−
transcription regulator, LacI family [imported],






putative


BI00546
142008
144242
−
4-alpha-glucanotransferase


BI00547
144506
144784
−
hypothetical protein Blon021648


BI00548
144856
145482
+
conserved hypothetical protein


BI00549
145500
146507
−
transcription regulator, LacI family [imported],






putative


BI00550
146777
147490
+
sugar ABC transporter, permease protein


BI00551
147605
150139
+
glycosyl hydrolase, family 31


BI00552
151125
153002
+
dnaK protein


BI00553
153005
153658
+
co-chaperone GrpE


BI00554
153753
154769
+
DnaJ protein [imported]


BI00555
154787
155371
+
hspR


BI00556
155647
156996
+
xanthine permease, putative


BI00557
157036
158154
+
possible acyl protein synthase/acyl-CoA






reductase-like protein


BI00558
158144
159640
+
possible acyl-CoA reductase


BI00559
159715
160497
+
3-oxoacyl-acyl carrier protein reductase


BI00560
160553
161281
+
beta-phosphoglucomutase, putative


BI00561
161435
162157
+
DedA protein


BI00749t
162383
163330
+
conserved hypothetical protein


BI00562
163340
164404
+
trbB


BI00751t
164410
165060
+
conserved hypothetical protein


BI00752t
165060
165659
+
hypothetical membrane protein with unknown






function


BI00563
165947
166231
+
hypothetical protein BL0505


BI00754t
166240
166614
+
conserved hypothetical protein


BI00564
166715
167041
+
conserved hypothetical protein


BI00565
167093
168220
+
BmrU protein, putative


BI00566
168424
169020
−
possible TetR-type transcriptional regulator


BI00567
169297
172125
+
DNA polymerase III, tau/gamma subunit


BI00568
172154
172753
+
recombination protein RecR


BI00569
172756
173886
−
sortase family protein


BI00570
174774
176054
+
conserved hypothetical protein


BI00571
176649
177179
+
hypothetical Amino acid kinase family


BI00572
177262
177801
+
aspartokinase, alpha and beta subunits


BI00573
177889
178980
−
aspartate-semialdehyde dehydrogenase


BI00574
179055
179765
+
conserved hypothetical protein


BI00575
179774
181351
−
Ser/Thr protein phosphatase family


BI00576
182040
183953
+
2-isopropylmalate synthase


BI00577
184031
186493
−
penicillin-binding protein, putative


BI00578
186772
187959
+
possible pre-pilin peptidase


BI00579
188086
191169
+
DNA topoisomerase I


BI00580
191549
192067
+
thymidylate kinase


BI00581
192067
193215
+
DNA polymerase III, delta subunit


BI00582
193337
193888
+
conserved hypothetical protein TIGR00481


BI00583
194034
195632
+
Unknown


BI00584
195767
197281
+
formate--tetrahydrofolate ligase


BI00585
197684
198028
−
conserved hypothetical protein


BI00586
198149
198763
+
narrowly conserved hypothetical membrane






protein


BI00587
198817
200226
−
hypothetical membrane protein with unknown






function


BI00588
200521
201177
+
phosphoglycerate mutase family protein


BI00589
201278
202228
+
conserved hypothetical protein


BI00590
202352
203224
+
transglycolase, epimerase


BI00591
203348
204496
−
extensin precursor (cell wall hydroxyproline-rich






glycoprotein)


BI00790t
204684
204866
+
hypothetical protein BL0470


BI00592
205053
206570
+
glutamyl-tRNA synthetase


BI00593
207503
207988
+
hypothetical protein Blon021299


BI00594
207946
208221
−
hypothetical protein BL0466


BI00595
208388
214285
+
cell wall surface anchor family protein, authentic






frameshift


BI00596
214390
215208
−
hypothetical


BI00597
216652
218460
+
conserved hypothetical integral membrane protein


BI00598
218637
219317
+
membrane antigen, putative


BI00599
219470
220744
+
Integral membrane protein


BI00600
220769
222070
+
possible permease protein of ABC transporter






system


BI00601
222107
223327
+
possible permease protein of ABC transporter






system


BI00602
223346
224140
+
ABC transporter, ATP-binding protein


BI00603
224259
224819
+
lipoprotein, putative


BI00604
224831
225427
−
transcriptional regulator, TetR family, putative


BI00605
225545
227704
−
phage infection protein, putative


BI00606
227704
230250
−
phage infection protein, putative


BI00607
230686
231969
+
membrane protein, putative


BI00608
232037
233602
+
6-phosphogluconate dehydrogenase,






decarboxylating


BI00609
233756
234595
−
6-phosphogluconolactonase


BI00610
234825
235847
−
oxppcycle protein OpcA


BI00611
235847
237499
−
glucose-6-phosphate 1-dehydrogenase


BI00612
237652
239337
+
Unknown


BI00613
239417
240448
−
Glycosyltransferase involved in cell wall






biogenesis


BI00614
240475
241311
−
transcriptional regulator, TetR family


BI00615
241407
242675
+
signal recognition particle-docking protein FtsY


BI00616
243046
244338
+
ammonium transporter


BI00617
244343
244678
+
Nitrogen regulatory protein P-II


BI00618
244832
246613
+
protein-pII, uridylyltransferase


BI00619
246653
248095
−
DNA-damage-inducible protein F, putative


BI00620
248301
249827
+
replicative DNA helicase


BI00621
249830
251299
+
UDP-N-acetylmuramyl tripeptide synthase


BI00622
251405
252154
+
cobyric acid synthase


BI00623
252306
252590
+
conserved hypothetical protein


BI00624
252590
254407
+
ABC1 family family


BI00625
254428
255447
−
transcriptional regulator, LacI family


BI00626
255933
257255
+
solute binding protein of ABC transporter system


BI00627
257546
258469
+
sugar ABC transporter, permease protein, putative


BI00628
258493
259308
+
ABC transporter, permease protein, MalFG






family


BI00629
259473
261446
+
conserved hypothetical protein


BI00630
262147
267966
+
hypothetical


BI00631
268074
271778
+
cell wall surface anchor family protein, putative


BI00632
271911
272741
+
conserved hypothetical protein TIGR00044


BI00633
272825
273835
−
prsA


BI00634
273960
274439
−
hypothetical COG3210: Large exoproteins






involved in heme utilization or adhesion


BI00635
274604
274891
+
ribosomal protein S6


BI00636
274951
275604
+
hypothetical single-strand binding protein


BI00637
275668
275913
+
ribosomal protein S18


BI00638
275936
276379
+
ribosomal protein L9


BI00639
276769
277026
+
ptsH


BI00640
277029
278705
+
phosphoenolpyruvate-protein phosphotransferase


BI00641
278942
279673
+
glycerol uptake facilitator protein


BI00642
279763
282468
−
copper-translocating P-type ATPase


BI00643
282580
282858
+
COG1937 family protein


BI00644
283012
284325
+
Uncharacterized BCR, YigN family, COG1322






family


BI00645
284325
284951
+
conserved hypothetical protein


BI00646
285048
285893
+
COG0566: rRNA methylases


BI00647
285787
286359
+
glutamyl-tRNA(Gln) amidotransferase, C subunit


BI00648
286366
287904
+
glutamyl-tRNA(Gln) amidotransferase, A subunit


BI00649
287933
289429
+
glutamyl-tRNA(Gln) amidotransferase, B subunit


BI00650
289728
290789
+
possible acetyltransferase


BI00651
290803
291114
+
conserved hypothetical protein


BI00652
291501
293141
+
conserved hypothetical protein


BI00653
293363
294973
+
BarJ


BI00654
295245
297248
+
transcription termination factor Rho


BI00655
297358
297501
+
hypothetical protein


BI00656
297559
297945
+
chorismate mutase


BI00657
298070
300151
+
cell wall surface anchor family protein, putative


BI00658
300383
303220
−
valyl-tRNA synthetase, putative


BI00659
303262
304686
−
ABC transporter, periplasmic substrate-binding






protein, putative


BI00660
304850
305533
−
endonuclease III


BI00661
305595
306374
−
transcriptional regulator


BI00662
306556
307212
−
membrane protein, putative


BI00663
307369
307950
−
integral membrane protein in the upf0059


BI00664
308187
308678
−
inorganic pyrophosphatase


BI00665
308908
311145
−
alpha-amylase family protein


BI00666
311386
313377
+
conserved hypothetical protein


BI00667
313988
315019
+
homoserine O-succinyltransferase


BI00668
315484
316293
+
ATP synthase F0, A subunit


BI00669
316400
316624
+
ATP synthase F0, C subunit


BI00670
316684
317199
+
ATP synthase F0, B subunit


BI00671
317237
318070
+
ATP synthase F1, delta subunit


BI00672
318149
319777
+
ATP synthase F1, alpha subunit


BI00673
319784
320704
+
ATP synthase F1, gamma subunit


BI00674
320716
322185
+
ATP synthase F1, beta subunit


BI00675
322188
322478
+
ATP synthase F1, epsilon subunit, putative


BI00676
322539
323336
+
Predicted nuclease of the RecB family


BI00677
323388
324374
−
possible secreted peptidyl-prolyl cis-trans






isomerase protein


BI00678
324455
325531
+
conserved hypothetical protein


BI00679
325534
326538
+
conserved hypothetical protein


BI00680
326790
327761
+
thioredoxin [imported], putative


BI00681
327850
328473
−
Adenylate cyclase


BI00682
329012
329398
+
endoribonuclease L-PSP, putative


BI00683
329536
330498
+
Acyltransferase domain protein


BI00684
330595
331593
+
glycerol-3-phosphate dehydrogenase, NAD-






dependent


BI00685
331783
332967
+
D-ala D-ala ligase


BI00686
333223
334386
+
ABC transporter, periplasmic substrate-binding






protein


BI00687
334206
335348
+
spermidine/putrescine ABC transporter, permease






protein, putative


BI00688
335348
336199
+
spermidine/putrescine ABC transporter, permease






protein, putative


BI00689
336207
337481
+
spermidine/putrescine ABC transporter, ATP-






binding protein


BI00690
337788
338828
+
CAAX amino terminal protease family protein






family


BI00691
338873
339667
−
Mechanosensitive ion channel family


BI00692
339751
341181
−
aspartate ammonia-lyase


BI00693
341302
342030
−
transcriptional regulator, TetR family domain






protein


BI00694
342124
343527
−
conserved hypothetical protein


BI00695
343852
344400
−
methylated-DNA--protein-cysteine






methyltransferase


BI00696
345228
346055
+
hypothetical protein with helix turn helix motif


BI00697
345928
347202
−
MFS transporter family protein, putative


BI00698
347393
348406
−
ribokinase [imported]


BI00939t
348735
349001
+
ribosomal protein L28


BI00699
349116
351944
+
ATP-dependent DNA helicase RecG


BI00700
352204
352782
+
methyltransferase, putative


BI00701
352812
353624
−
tRNA (guanine-N1)-methyltransferase


BI00702
353623
355341
+
Unknown


BI00703
355422
356399
+
conserved hypothetical protein


BI00704
356482
357354
+
4-diphosphocytidyl-2C-methyl-D-erythritol






synthase, putative


BI00705
357367
358041
+
pyrrolidone-carboxylate peptidase, putative


BI00706
358303
359766
+
IgA-specific serine endopeptidase, putative


BI00707
359884
361224
+
aminopeptidase C


BI00708
361519
362649
+
phospho-2-dehydro-3-deoxyheptonate aldolase


BI00709
362781
364010
+
phospho-2-dehydro-3-deoxyheptonate aldolase


BI00710
364141
364845
+
MTA/SAH nucleosidase


BI00711
365444
366427
+
hypothetical ATPase, histidine kinase-, DNA






gyrase B-, and HSP90-like domain protein


BI00712
366563
367330
+
DNA-binding response regulator RegX3


BI00713
367583
368713
+
phosphate ABC transporter, phosphate-binding






protein


BI00714
368927
369877
+
pstC2


BI00715
369997
370875
+
phosphate ABC transporter, permease protein


BI00716
370931
371707
+
phoT


BI00717
372005
372580
+
lemA protein


BI00718
372647
374902
+
conserved hypothetical protein


BI00719
374971
375831
+
oxidoreductase, aldo/keto reductase family


BI00720
375932
376981
+
inosine-uridine preferring nucleoside hydrolase


BI00721
377109
377729
−
16S rRNA processing protein RimM


BI00722
377755
377985
−
KH domain protein


BI00723
378009
378467
−
ribosomal protein S16


BI00724
378703
379809
−
Endonuclease/Exonuclease/phosphatase family






family


BI00725
379889
381634
−
signal recognition particle protein


BI00726
381843
382748
+
cation efflux family protein superfamily


BI00727
382773
384488
−
cysteinyl-tRNA synthetase


BI00728
384518
385363
+
possible amidotransferase


BI00729
385627
387687
+
ABC transporter, ATP-binding protein


BI00730
387746
388162
−
plasmid stability protein StbB


BI00731
388175
388450
−
hypothetical protein


BI00732
388609
389160
−
acetolactate synthase, small subunit


BI00733
389180
391144
−
acetolactate synthase, large subunit, biosynthetic






type


BI00734
391308
392033
−
ribonuclease III


BI00735
392189
392380
−
ribosomal protein L32


BI00736
392472
393098
−
Uncharacterized ACR, COG1399


BI00737
393191
394078
−
conserved hypothetical protein


BI00738
394089
394586
−
pantetheine-phosphate adenylyltransferase


BI00739
394860
395150
+
conserved hypothetical protein


BI00740
395198
396205
−
K+ channel, beta subunit


BI00741
396379
396804
+
transcription regulator, MerR family NMB1303






[imported], putative


BI00742
396910
397533
−
hypothetical transmembrane protein with






unknown function


BI00743
397764
399083
+
nicotinate phosphoribosyltransferase, putative


BI00744
399381
400142
+
ribonuclease PH


BI00745
400189
400944
+
Ham1 family


BI00746
401106
402659
+
hypothetical FemAB family


BI00747
402736
404043
+
FemAB family protein, putative


BI00748
404096
405373
+
beta-lactam resistance factor, putative


BI00749
405462
406460
−
membrane protein, putative


BI00750
407182
408879
+
glucose-6-phosphate isomerase


BI00751
409515
409877
+
ribosomal protein L19


BI00752
410047
410901
+
lepB


BI00753
411024
411860
+
ribonuclease HII


BI00754
411990
413102
+
transcription regulator, LacI family [imported]


BI00755
413261
414904
+
probable sugar kinase


BI00756
414992
415681
+
sugar isomerase


BI00757
416114
417430
+
L-arabinose isomerase


BI00758
417620
418240
−
trp-G type glutamine






amidotransferase/dipeptidase


BI00759
418178
420178
+
membrane protein, putative


BI00760
420330
421694
+
permease, putative


BI00761
421694
422914
+
transmembrane protein Vexp1, putative


BI00762
422930
423562
+
Vexp2


BI00763
423886
425706
−
long-chain-fatty-acid--CoA ligase, putative


BI00764
425820
426098
+
fragment of arabinose permease


BI00765
426765
429890
+
hypothetical ABC transporter


BI00766
430170
430436
−
major facilitator family transporter CC0814






[imported], putative


BI00767
431272
432618
+
solute binding protein of ABC transporter system


BI00768
432750
433799
+
sugar ABC transporter, permease protein, putative


BI00769
433820
434809
+
Unknown


BI00770
435125
437128
+
beta-D-galactosidase, putative


BI00771
437175
438227
+
transcription regulator, LacI family [imported],






putative


BI00772
438426
441116
+
arabinogalactan endo-1,4-beta-galactosidase,






putative


BI00773
441755
442621
+
oxidoreductase, aldo/keto reductase family


BI00774
442628
443368
+
conserved hypothetical protein


BI00775
443378
444745
−
conserved hypothetical protein


BI00776
445003
446367
+
transport protein, NRAMP family


BI00777
446472
448073
−
drug resistance transporter, EmrB/QacA






subfamily


BI00778
448424
450007
+
glycosyl transferase CpsE


BI00779
450302
452029
+
COG0840: Methyl-accepting chemotaxis protein


BI00780
452064
453566
+
possible Etk-like tyrosine kinase involved in Eps






biosynthesis


BI00781
453760
454725
+
hypothetical glycosyl transferase, group 1 family






protein


BI00782
454725
456065
+
putative glycosyltransferase protein


BI00783
456065
457126
+
NAD dependent epimerase/dehydratase family






protein


BI00784
457201
458448
+
UDP-glucose 6-dehydrogenase


BI00785
458489
459550
+
hypothetical glycosyl transferase, group 1 family






protein


BI00786
459581
460408
+
hypothetical Eps11I


BI00787
460446
460952
+
hypothetical Bacterial transferase hexapeptide






(three repeats)


BI00788
460985
461998
+
hypothetical Capsular polysaccharide synthesis






protein


BI00789
462020
463360
+
hypothetical protein


BI00790
463363
464292
+
Eps9K


BI00791
464362
465753
+
hypothetical Polysaccharide biosynthesis protein


BI00792
465789
466280
+
hypothetical Bacterial transferase hexapeptide






(three repeats)


BI00793
466366
467514
−
NAD-dependent epimerase/dehydratase family






protein, putative


BI00794
467785
468363
−
transposase, degenerate


BI00795
468615
468770
−
hypothetical COG2963: Transposase and






inactivated derivatives


BI00796
469189
470208
+
dTDP-glucose 4,6-dehydratase


BI00797
470347
471303
+
dTDP-4-dehydrorhamnose 3,5-epimerase


BI00798
471349
472245
+
glucose-1-phosphate thymidylyltransferase


BI00799
472858
473046
−
hypothetical protein


BI00800
473371
473802
−
conserved hypothetical protein


BI00801
474083
474640
−
hypothetical Low molecular weight






phosphotyrosine protein phosphatase


BI00802
474825
475331
−
hypothetical protein


BI00803
475655
475867
−
hypothetical Helix-turn-helix


BI00804
475860
476042
−
hypothetical protein


BI00805
475971
476312
+
hypothetical protein


BI00806
476415
477422
−
conserved hypothetical protein


BI00807
477471
478751
+
narrowly conserved hypothetical protein


BI00808
477495
477866
−
thioredoxin


BI00809
478880
479734
+
3-oxoadipate enol-lactonase, putative


BI00810
479747
481036
+
MutT/nudix family protein


BI00811
481065
481475
+
glycine cleavage system H protein


BI00812
481547
482875
+
conserved hypothetical protein


BI00813
482973
485453
+
protease II


BI00814
485521
486549
+
3-isopropylmalate dehydrogenase


BI00815
486610
487692
+
lipoate-protein ligase a


BI00817
487934
488650
+
probable transcriptional regulator with cyclic






nucleotide-binding domain


BI00818
488757
491069
+
ponA, putative


BI00819
491264
492634
+
NADH-dependent flavin oxidoreductase, putative


BI00820
492807
493955
−
dihydroorotate dehydrogenase, putative


BI00821
494409
495122
+
glycerol-3-phosphate regulon repressor


BI00822
495118
496365
+
galactose-1-phosphate uridylyltransferase


BI00823
496241
497632
+
galactokinase


BI00824
497718
497987
+
ACT domain protein


BI00825
498201
499487
+
similar to unknown proteins


BI00826
499800
500516
−
spoU


BI00827
500612
501463
+
mutY


BI00828
501531
502250
+
conserved hypothetical protein


BI00829
502633
505968
+
DNA-directed RNA polymerase, beta subunit


BI00830
506139
510173
+
DNA-directed RNA polymerase, beta-prime






subunit


BI00831
510338
510967
−
FHA domain protein


BI00832
510986
511498
−
hypothetical protein Blon020438


BI00833
511528
512457
−
possible phosphoprotein phosphatase


BI00834
512457
514967
−
membrane protein, putative


BI00835
514967
516187
−
Protein of unknown function family


BI00836
516215
517585
−
moxR2


BI00837
517599
523580
−
cell wall surface anchor family protein, putative


BI00838
523750
525168
−
serine/threonine protein kinase, putative


BI00839
525300
529592
+
hypothetical COG0210: Superfamily I DNA and






RNA helicases


BI00840
529427
533620
+
UvrD/REP helicase domain protein


BI00841
533962
535152
+
possible transport protein


BI00842
535527
536243
+
dihydrodipicolinate reductase


BI00843
536388
537311
+
dihydrodipicolinate synthase


BI00844
537585
539246
+
metallo-beta-lactamase superfamily protein


BI00845
539291
541897
+
Peptidase family M1 domain protein


BI00846
542078
542971
+
hypothetical transmembrane protein with






unknown function


BI00847
543164
543502
+
conserved hypothetical protein


BI00848
543954
545336
+
phosphoglucosamine mutase


BI00849
545362
546012
+
polypeptide deformylase


BI00850
546072
547472
+
conserved hypothetical protein


BI00851
547492
547620
+
hypothetical protein


BI00852
547858
548979
+
peptide chain release factor 2


BI00853
548991
550121
+
ftsE


BI00854
550135
551055
+
cell division ABC transporter, permease protein






FtsX, putative


BI00855
551161
552519
+
autolysin, putative


BI00856
552673
553146
+
SsrA-binding protein


BI00857
553192
554265
+
amino acid ABC transporter, permease protein


BI00858
554479
555420
+
amino acid ABC transporter, permease protein


BI00859
555554
556546
+
amino acid ABC transporter, permease protein


BI00860
556566
557393
+
glutamine ABC transporter, ATP-binding protein


BI00861
557604
559493
+
glucosamine--fructose-6-phosphate






aminotransferase, isomerizing


BI00862
559699
560271
+
COG0564: Pseudouridylate synthases, 23S RNA-






specific


BI00863
560313
560525
−
hypothetical protein Blon020898


BI00864
560565
561548
−
transcriptional regulator, LacI family, putative


BI00865
561794
562717
+
sugar ABC transporter, permease protein, putative


BI00866
562776
563780
+
Unknown


BI00867
563975
566047
+
beta-D-galactosidase


BI00868
566259
567185
+
transcriptional regulator, LacI family, putative


BI00869
567311
569008
−
alpha-L-arabinofuranosidase


BI00870
569168
570517
+
solute binding protein of ABC transporter system


BI00871
570852
572192
+
probable solute binding protein of ABC






transporter system for sugars


BI00872
572449
573729
+
sugar binding protein Sbp


BI00873
573795
574562
−
transcription activator, probable Baf family






[imported]


BI00874
574688
576304
+
ABC transporter, periplasmic substrate-binding






protein, putative


BI00875
576372
577346
+
membrane protein, putative


BI00876
577346
578245
+
peptide ABC transporter, permease protein,






putative


BI00877
578245
579033
+
ABC transporter, nucleotide binding/ATPase






protein


BI00878
579029
579811
+
ABC transporter, ATP-binding protein


BI00879
580296
581360
+
cystathionine beta-synthase


BI00880
581455
582636
+
cystathionine beta-lyase


BI00881
582780
584501
−
ErfK/YbiS/YcfS/YnhG family


BI00882
584781
586613
+
ATP-dependent DNA helicase RecQ


BI00883
586729
587220
+
autoinducer-2 production protein LuxS


BI00884
587453
587917
+
acetyltransferase, GNAT family, putative


BI00885
588181
589638
−
hypothetical protein Blon020876


BI00886
589890
591347
−
amino acid permease


BI00887
591542
592891
+
alanine racemase


BI00888
593087
594370
+
deoxyguanosinetriphosphate triphosphohydrolase,






putative


BI00889
594546
596642
+
DNA primase, putative


BI00890
596961
597710
+
pyridoxine biosynthesis protein


BI00891
597799
598434
+
SNO glutamine amidotransferase family






superfamily


BI00892
598495
600156
+
aminotransferase, class I, putative


BI00893
600514
601443
+
asparaginase family protein


BI00894
601476
601607
+
hypothetical protein Blon020867


BI00895
601574
601897
−
hypothetical protein


BI00896
601995
603179
+
possible transport protein


BI00897
603210
603467
−
hypothetical protein Blon020865


BI00898
603634
603723
+
hypothetical protein


BI00899
603651
605795
−
similar to alpha-L-arabinofuranosidase A


BI00900
605923
606921
+
EF0065, putative


BI00901
607014
608087
−
conserved hypothetical protein


BI00902
608687
609373
+
ABC transporter, ATP-binding protein


BI00903
609373
610545
+
conserved hypothetical protein


BI00904
610560
612116
+
ABC transporter, ATP-binding protein


BI00905
612106
614304
−
1-deoxyxylulose-5-phosphate synthase


BI00906
614478
615467
+
oxidoreductase, zinc-binding, putative


BI00907
615572
616069
+
phosphoribosylaminoimidazole carboxylase,






catalytic subunit


BI00908
616095
617231
+
phosphoribosylaminoimidazole carboxylase,






ATPase subunit


BI00909
617243
617668
+
furB


BI00910
617709
617954
−
conserved hypothetical protein


BI00911
618183
619103
+
possible solute binding protein of ABC






transporter system


BI00912
619367
621439
+
membrane protein, putative


BI00913
621563
623197
+
aldehyde dehydrogenase


BI00914
623577
624842
−
phosphoribosylamine--glycine ligase


BI00915
624872
625702
−
phosphoribosylformylglycinamidine cyclo-ligase


BI00916
626029
627537
−
amidophosphoribosyltransferase


BI00917
627944
628726
−
glutamine ABC transporter, ATP-binding protein


BI00918
628726
629610
−
amino acid ABC transporter, permease protein


BI00919
629723
630583
−
amino acid ABC transporter, periplasmic amino






acid-binding protein


BI00920
630788
631255
−
conserved hypothetical protein


BI00921
631328
632698
−
Atz/Trz family protein, putative


BI00922
632741
634240
−
S-adenosyl-L-homocysteine hydrolase, NAD






binding domain


BI00923
634405
635991
+
structural gene for ultraviolet resistance


BI00924
635991
636206
+
hypothetical protein Blon020836


BI00925
636246
637220
−
K+ channel, beta subunit


BI00926
637331
638293
−
transcriptional regulator, HTH_1 family, putative


BI00927
638512
640023
+
Na+/H+ antiporter, putative


BI00928
640043
640699
−
membrane protein, putative


BI00929
640699
642066
−
conserved hypothetical protein


BI00930
642042
643337
−
possible carboxylesterase or lipase


BI00931
643478
647209
−
phosphoribosylformylglycinamidine synthase


BI00932
647275
648024
−
phosphoribosylaminoimidazole-






succinocarboxamide synthase


BI00933
648113
648232
−
hypothetical protein


BI00934
648420
649754
−
phosphoribosylglycinamide formyltransferase 2






VC1228 [imported]


BI00935
649928
651085
+
type 1 capsular polysaccharide biosynthesis






protein J (capJ)


BI00936
651238
652260
−
conserved hypothetical protein


BI00937
652822
653880
+
transporter


BI00938
654695
654967
+
ribosomal protein S12


BI00939
654976
655443
+
ribosomal protein S7


BI00940
655478
657598
+
translation elongation factor G


BI00941
657774
658970
+
translation elongation factor Tu


BI00942
659184
659909
+
conserved hypothetical protein


BI00943
660169
660864
+
transcriptional regulator, LysR family, putative


BI00944
661085
662098
+
membrane protein, putative


BI00945
662161
662637
−
COG2246: Predicted membrane protein


BI00946
662721
663083
−
CrcB protein


BI00947
663086
663619
−
protein with similarity to CrcB


BI00948
663706
663987
+
hypothetical protein


BI00949
664023
665063
+
alcohol dehydrogenase, zinc-containing


BI00950
665437
665625
+
hypothetical protein


BI00951
665652
667028
−
conserved hypothetical protein


BI00952
667295
667462
−
possible MarR-type transcriptional regulator


BI00953
667902
670487
+
excinuclease ABC, subunit A


BI00954
670548
671903
+
MATE efflux family protein, putative


BI00955
671914
672603
+
endonuclease III, putative


BI00956
672783
673076
−
hypothetical protein Blon020400


BI00957
673098
673766
+
Unknown


BI00958
673782
674042
−
hexapeptide-repeat containing-acetyltransferase


BI00959
674207
675292
+
possible integral membrane permease protein


BI00960
675273
675902
+
hypothetical Glycosyl hydrolases family 2, TIM






barrel domain


BI00961
676090
677316
−
glutamine synthetase, type I


BI00962
677846
678625
−
narrowly conserved hypothetical transmembrane






protein


BI00963
678712
680199
−
dihydrolipoamide dehydrogenase


BI00964
680351
680971
−
conserved hypothetical protein


BI00965
681063
682427
+
widely conserved protein in peptidase or






deacetlylase family


BI00966
682730
683326
+
conserved hypothetical protein


BI00967
683329
684801
+
ABC transporter, ATP-binding protein, putative


BI00968
684801
685625
+
possible permease protein of ABC transporter for






cobalt


BI00969
685824
686699
+
spoU rRNA methylase family protein [imported]


BI00970
686891
687820
+
phenylalanyl-tRNA synthetase, alpha subunit


BI00971
687831
690437
+
phenylalanyl-tRNA synthetase, beta subunit


BI00972
690471
691154
+
conserved hypothetical protein


BI00973
691385
692347
+
N-acetyl-gamma-glutamyl-phosphate reductase


BI00974
692434
693519
+
arginine biosynthesis bifunctional protein ArgJ


BI00013g
693503
693979
−
hypothetical protein Magn025872


BI00975
693809
694612
+
acetylglutamate kinase


BI00976
694605
695897
+
acetylornithine aminotransferase


BI00977
695944
696906
+
ornithine carbamoyltransferase


BI00978
696906
697415
+
arginine repressor


BI00979
697501
698736
+
argininosuccinate synthase


BI00980
699184
700653
+
argininosuccinate lyase


BI01326t
701005
701196
+
thiamine biosynthesis protein ThiS


BI00981
701211
702077
+
thiG protein


BI00982
702157
702963
+
moeB


BI00983
703023
703376
+
rhodanese-like domain protein


BI00984
703541
704071
+
HD domain protein


BI00985
703978
704835
+
hypothetical


BI00986
704964
706283
+
tyrosyl-tRNA synthetase


BI00987
706314
708086
+
hypothetical protein BL1050


BI00988
708098
709135
+
Predicted sugar phosphatases of the HAD






superfamily


BI00989
709395
710165
+
hemolysin A


BI00990
710153
710719
−
conserved hypothetical protein


BI00991
710729
710881
+
hypothetical protein


BI00992
710965
711624
−
similar to a bacterial K(+)-uptake system


BI00993
711678
713141
−
Cation transport protein domain protein


BI00994
713388
714407
+
poly(P)/ATP-NAD kinase


BI00995
714410
716233
+
DNA repair protein RecN


BI00996
716266
716910
+
hydrolase, haloacid dehalogenase-like family,






putative


BI00997
717154
717525
+
transcriptional regulator, GntR family


BI00998
717550
718467
+
ABC transporter, ATP-binding protein


BI01351t
718477
719091
+
membrane protein, putative


BI00999
719985
722768
−
calcium-translocating P-type ATPase, PMCA-






type


BI01000
722966
723238
+
hypothetical protein BL1037


BI01001
723291
724778
−
threonine synthase


BI01356t
725001
725699
+
serine hydroxymethyltransferase


BI01002
726028
727116
+
gamma-glutamyl phosphate reductase


BI01003
727134
727694
+
conserved hypothetical protein


BI01004
727694
728476
+
nicotinate (nicotinamide) nucleotide






adenylyltransferase


BI01005
728580
729857
−
glycosyl hydrolase, family 3, putative


BI01006
729952
733203
+
Uncharacterized ACR


BI01007
733340
733834
+
phosphinothricin acetyltransferase


BI01008
734033
734629
+
peptidyl-tRNA hydrolase


BI01009
734622
738203
+
transcription-repair coupling factor


BI01010
738346
739290
+
oxidoreductase, putative


BI01011
739444
740739
+
enolase


BI01012
740809
741423
+
hypothetical Septum formation initiator


BI01013
741423
741986
+
conserved hypothetical protein


BI01014
742052
743050
+
possible exopolyphosphatase-like protein


BI01015
743578
744711
+
IS30 family, transposase [imported]


BI01016
744846
747062
+
L-serine dehydratase 1


BI01018
747207
747611
+
peptidyl-prolyl cis-trans isomerase, FKBP-type


BI01019
747713
748189
+
transcription elongation factor GreA


BI01020
748250
749191
−
hemolysin, putative


BI01021
749361
750086
+
conserved hypothetical protein


BI01022
750474
751736
+
histidine kinase-like protein


BI01023
751815
752090
−
hypothetical Transcription factor WhiB


BI01024
752207
753922
−
diarrheal toxin


BI01025
754203
755633
−
Transcriptional regulator


BI01389t
755884
756180
+
whiB1


BI01026
756350
759319
+
membrane protein, putative


BI01027
759319
760857
+
LPXTG-motif cell wall anchor domain protein,






putative


BI01028
760966
761391
−
conserved hypothetical protein


BI01029
761660
762283
+
conserved hypothetical protein


BI01030
762332
763015
+
Phosphoribosyl transferase domain protein


BI00019g
762937
763509
−
hypothetical Peptidase family S24


BI01031
763391
764464
−
sensory box histidine kinase, putative


BI01032
764464
765183
−
DNA-binding response regulator MtrA


BI01033
765222
767432
−
1,4-alpha-glucan branching enzyme


BI01034
767649
768239
+
possible transcriptional regulator


BI01035
768351
768872
+
2C-methyl-D-erythritol 2,4-cyclodiphosphate






synthase


BI01036
768930
769760
−
zinc ABC transporter, permease protein, putative


BI01037
769830
770834
−
ABC transporter, ATP-binding protein


BI01038
770893
772419
−
possible solute binding protein of ABC






transporter system


BI01039
772190
773062
+
methylenetetrahydrofolate






dehydrogenase/methenyltetrahydrofolate






cyclohydrolase


BI01040
773185
774657
+
ribosomal protein S1 [imported]


BI01041
774834
775448
+
dephospho-CoA kinase


BI01042
775463
777571
+
excinuclease ABC, B subunit


BI01043
777887
778726
+
TerC family protein [imported]


BI01044
778897
780336
+
pyruvate kinase


BI01045
780490
781086
−
possible NTP pyrophosphatase in MutT family


BI01046
781432
782214
+
response regulator


BI01047
782278
785127
+
DNA polymerase I


BI01048
785291
786217
+
conserved hypothetical protein TIGR00486


BI01049
786266
786937
+
MutT/nudix family protein, putative


BI01050
787135
789132
+
glycogen operon protein GlgX


BI01424t
789186
789413
+
hypothetical protein with helix turn helix motif


BI01051
789420
790067
+
conserved hypothetical protein


BI01052
790243
790794
−
DNA-3-methyladenine glycosylase I


BI01053
791884
792942
−
hypothetical protein


BI01054
793226
793780
+
hypothetical protein


BI01055
793761
794246
−
hypothetical protein


BI00021g
794049
794498
+
transposase B


BI00020g
794300
794749
+
IS1601-D


BI01056
794665
794844
+
transposase subunit B


BI01057
794937
795989
−
integrase/recombinase XerC, probable [imported],






putative


BI01434t
795989
796876
−
probable integrase/recombinase


BI01058
796951
798150
−
probable integrase/recombinase


BI01059
798284
799564
−
IS3-Spn1, transposase


BI01060
799635
800477
−
putative transposase subunit


BI01061
800762
802579
−
hypothetical Protein of unknown function






DUF262


BI01062
802742
803464
−
hypothetical protein


BI01063
803748
804065
−
conserved hypothetical protein


BI01064
804058
804405
−
hypothetical protein


BI01065
804667
808221
+
DNA polymerase III, alpha chain VC2245






[imported]


BI01066
808312
808743
+
conserved hypothetical protein


BI01067
808952
810826
+
antigen, 67 kDa


BI01068
810916
811413
+
NH2-acetyltransferase


BI01069
817553
818377
−
oxidoreductase, aldo/keto reductase family


BI01070
818538
819956
+
sugar kinase, FGGY family, putative


BI01451t
819972
820262
+
Acylphosphatase


BI01071
820382
821761
+
histidinol dehydrogenase


BI01072
821761
822918
+
histidinol-phosphate aminotransferase


BI01073
823007
823603
+
imidazoleglycerol-phosphate dehydratase


BI01074
823606
824397
+
hypothetical protein Blon020586


BI01075
824435
825079
+
imidazole glycerol phosphate synthase, glutamine






amidotransferase subunit


BI01076
825152
825874
+
bifunctional HisA/TrpF protein


BI01077
825984
826103
−
narrowly conserved hypothetical protein


BI01463t
826039
827637
−
conserved hypothetical protein


BI01078
827738
828898
+
Glutamine synthetase, catalytic domain


BI01079
829137
829604
+
transporter, putative


BI01080
829657
830625
−
conserved hypothetical protein


BI01081
830625
834758
−
ATP-dependent helicase HrpA


BI01082
834751
835404
−
conserved hypothetical protein


BI01083
835647
837065
+
GTP-binding protein


BI01084
837405
838208
+
L-lactate dehydrogenase


BI01085
838356
839291
−
cation efflux system protein


BI01086
839460
840182
−
LexA repressor


BI01087
840333
840680
+
LysM domain protein


BI01088
840736
841173
+
conserved hypothetical protein TIGR00244


BI01089
841314
842510
−
D-3-phosphoglycerate dehydrogenase


BI01090
842524
844800
−
COG3973: Superfamily I DNA and RNA






helicases


BI01091
845133
845651
+
conserved hypothetical protein TIGR00242


BI01092
845654
846730
+
S-adenosyl-methyltransferase MraW


BI01093
846740
847186
+
hypothetical protein Blon020568


BI01094
847186
848985
+
penicillin-binding protein, putative


BI01095
849015
849884
+
conserved hypothetical protein


BI01096
849936
851384
+
UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-






diaminopimelate--D-alanyl-D-alanyl ligase


BI01097
851453
852535
+
phospho-N-acetylmuramoyl-pentapeptide-






transferase


BI01098
852593
854035
+
UDP-N-acetylmuramoylalanine--D-glutamate






ligase


BI01099
854025
855239
+
cell division protein, FtsW/RodA/SpoVE family,






putative


BI01100
855258
856436
+
UDP-N-acetylglucosamine--N-acetylmuramyl-






(pentapeptide) pyrophosphoryl-undecaprenol N-






acetylglucosamine transferase


BI01101
856651
858075
+
UDP-N-acetylmuramate--alanine ligase


BI01102
858078
859139
+
hypothetical Cell division protein FtsQ


BI01103
859565
860983
+
hypothetical Appr-1-p processing enzyme family


BI01104
861241
861813
+
unknown


BI01105
861640
861885
−
hypothetical protein


BI01106
861906
862391
+
D-tyrosyl-tRNA(Tyr) deacylase


BI01107
862494
863735
−
glucose/galactose transporter, putative


BI01108
863844
864230
−
hypothetical glyoxalase family protein


BI01109
864308
865201
−
fructokinase, putative


BI01110
865277
866488
−
transcription regulator ROK family VC2007






[imported], putative


BI01111
866715
867626
+
glucokinase, putative


BI01112
867792
868913
−
NagC/XylR-type transciptional regulator


BI01113
869251
870060
+
glucosamine-6-phosphate isomerase


BI01114
870119
871393
+
N-acetylglucosamine-6-phosphate deacetylase


BI01115
871646
873307
+
dipeptide ABC transporter, dipeptide-binding






protein


BI01116
873480
874568
+
oligopeptide ABC transporter, permease protein


BI01117
874714
875739
+
dipeptide ABC transporter, permease protein


BI01118
875746
877452
+
ATP binding protein of ABC transporter


BI01119
877508
878026
−
MutT/nudix family protein


BI01120
878078
879670
−
Xaa-Pro aminopeptidase I


BI01121
879977
880954
−
conserved hypothetical protein


BI01122
882044
883672
+
folC


BI01123
883736
887410
+
SMC family, C-terminal domain family


BI01124
887535
888527
−
conserved hypothetical protein


BI01125
888652
890202
−
UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-






diaminopimelate ligase


BI01126
890377
891126
+
RNA polymerase sigma-70 factor, ECF subfamily


BI01127
891129
891446
+
conserved hypothetical protein


BI01128
891719
892660
−
Aldose 1-epimerase superfamily


BI01129
892788
893741
−
Aldose 1-epimerase superfamily


BI01130
894032
895021
+
hydroxymethylbutenyl pyrophosphate reductase


BI01131
895067
895573
−
transcriptional regulator, putative


BI01132
895670
896725
−
glyceraldehyde-3-phosphate dehydrogenase, type I


BI01133
896968
897690
−
Thiamin pyrophosphokinase, catalytic domain






family


BI01134
897586
898923
+
hypothetical Spermine/spermidine synthase


BI01135
899364
899930
+
Translation initiation factor IF-3, C-terminal






domain


BI00041g
899764
900105
+
ribosomal protein L35


BI01136
900161
900541
+
ribosomal protein L20


BI01137
900605
901537
+
Integrase


BI01138
901668
904511
+
ABC transporter, ATP-binding protein


BI01139
904656
905612
+
Soj family protein


BI01140
905634
906545
+
Uncharacterised ACR, COG1354


BI01141
906675
907274
+
conserved hypothetical protein TIGR00281


BI01142
907409
908233
+
MutT/nudix family protein


BI01143
908296
909573
+
quinolinate synthetase complex, A subunit


BI01144
909668
911296
+
L-aspartate oxidase


BI01145
911303
912193
+
nicotinate-nucleotide pyrophosphorylase


BI01146
912292
913443
+
possible pyridoxal-phosphate-dependent






aminotransferase


BI01147
913478
914824
+
major facilitator family transporter


BI01148
915142
917070
+
GTP-binding protein TypA


BI01149
917197
917616
+
conserved hypothetical protein


BI01150
917699
918673
+
prephenate dehydratase, putative


BI01151
918670
919734
+
prephenate dehydrogenase


BI01152
919947
920201
+
conserved hypothetical protein


BI01153
920239
921303
+
phage integrase family protein


BI01154
921559
923196
+
solute binding protein of ABC transporter system






possibly for peptides


BI01155
923500
924423
+
dppB


BI01156
924445
925446
+
dppC


BI01157
925505
927478
+
ABC-type transporter, duplicated ATPase






component


BI01158
927793
928650
−
exodeoxyribonuclease III


BI01159
928775
929626
+
conserved hypothetical protein


BI01160
929645
930400
+
narrowly conserved hypothetical transmembrane






protein


BI01161
930393
931658
+
RNA methyltransferase, TrmA family


BI01162
931673
932365
+
lipoprotein, putative


BI01163
932483
935032
+
cation-transporting ATPase, E1-E2 family


BI01164
935156
937852
+
aconitate hydratase 1


BI01165
938001
938360
+
Ribbon-helix-helix protein, copG family domain






protein


BI01166
938363
938851
+
PIN domain, putative


BI01167
938917
941019
−
Protein of unknown function DUF262 family


BI01168
941112
941777
−
acetyltransferase, GNAT family family


BI01169
941793
942608
−
DNA-binding response regulator, putative


BI01170
942553
943935
−
atypical histidine kinase sensor of two-component






system


BI01171
944117
944959
+
conserved hypothetical protein


BI01172
945143
946039
+
membrane protein, putative


BI01173
946326
947195
+
membrane protein, putative


BI01174
947234
948073
−
GTP pyrophosphokinase [imported]


BI01175
948115
949554
+
tRNA-i(6)A37 thiotransferase enzyme MiaB


BI01176
949568
950551
+
tRNA delta(2)-isopentenylpyrophosphate






transferase


BI01177
950591
951517
−
Fic protein family family


BI01178
951663
954437
+
cell division protein FtsK


BI01179
954635
955267
+
CDP-diacylglycerol--glycerol-3-phosphate 3-






phosphatidyltransferase


BI01180
955282
955812
+
competence/damage-inducible protein CinA






domain protein


BI01181
955881
956387
+
possible DNA binding protein


BI01182
956502
956732
+
conserved hypothetical protein


BI01183
957036
958226
+
recA protein


BI01184
958232
958822
+
regulatory protein RecX


BI01185
959702
960361
+
S30AE family protein


BI01186
960556
963417
+
preprotein translocase, SecA subunit


BI00044g
963734
963970
−
COG3464: Transposase and inactivated






derivatives


BI01187
963974
964096
−
COG3464: Transposase and inactivated






derivatives


BI00045g
964219
964602
+
hypothetical protein BL0497


BI01188
964674
965717
+
anthranilate phosphoribosyltransferase


BI01189
965964
966686
−
hypothetical transmembrane protein with






unknown function


BI01190
966447
967418
+
hypothetical Acyltransferase


BI01191
967476
969722
−
serine/threonine protein kinase, putative


BI01192
969893
970858
−
idsA2


BI01193
971179
971838
+
conserved hypothetical protein


BI01194
972002
973465
+
RNA polymerase principal sigma factor, sigma 70


BI01195
973526
975799
+
DNA gyrase, subunit B


BI01196
975969
977192
+
membrane protein, putative


BI01197
977269
978228
+
ribokinase


BI01198
978247
982977
+
DEAD/DEAH box helicase domain protein


BI01199
982994
983779
−
DNA-binding response regulator TcrA, putative


BI01200
983927
986953
−
DNA gyrase A subunit


BI01201
986925
988169
+
conserved hypothetical protein


BI01202
988185
989189
−
conserved hypothetical protein


BI01203
989432
989722
+
conserved hypothetical protein


BI01204
989725
990198
+
deoxyuridine 5triphosphate nucleotidohydrolase


BI01205
990335
992656
+
GTP pyrophosphokinase


BI01206
992780
993058
−
orfB


BI01207
993226
994425
+
probable integrase/recombinase


BI01640t
994500
995387
+
probable integrase/recombinase


BI01208
995387
996439
+
integrase/recombinase XerC, probable [imported],






putative


BI01209
996532
997095
−
COG2801: Transposase and inactivated






derivatives


BI00053g
997107
997619
−
ASOPSNART-11OSRSI


BI01210
997719
998264
−
possible peptidyl-prolyl cis-trans isomerase


BI01211
998331
999296
−
COG3391: Uncharacterized conserved protein


BI01212
999519
999623
−
hypothetical protein


BI01213
999683
1000615
−
membrane protein, putative


BI01214
1000747
1001295
+
Hypothetical cytosolic protein


BI01215
1001329
1002621
−
conserved hypothetical protein


BI01216
1002648
1003532
+
possible phosphoglycerate mutase


BI01217
1003650
1004597
+
magnesium transporter, CorA family


BI01218
1004615
1005538
+
glnH, putative


BI01219
1005776
1008544
+
leucyl-tRNA synthetase


BI01220
1008708
1009484
+
competence protein ComEA helix-hairpin-helix






repeat region domain protein


BI01221
1009553
1011235
+
conserved hypothetical transmembrane protein






related to ComA


BI01222
1011378
1012721
+
possible prolidase (X-Pro dipeptidase) or






chlorohydrolase


BI01223
1012791
1013759
+
conserved hypothetical protein


BI01224
1013783
1014346
+
conserved hypothetical protein TIGR00150


BI01225
1014411
1015289
+
conserved hypothetical protein


BI01226
1015308
1015859
+
ribosomal-protein-alanine acetyltransferase


BI01227
1015859
1016899
+
O-sialoglycoprotein endopeptidase


BI01228
1017438
1017539
−
hypothetical protein


BI01229
1017569
1018501
+
probable integrase/recombinse


BI01230
1018564
1018887
−
conserved hypothetical protein


BI01231
1018909
1019787
−
conserved hypothetical protein


BI01232
1019849
1020361
−
conserved hypothetical protein


BI01233
1020474
1021376
−
Fic protein family family


BI01234
1021357
1021929
−
hypothetical protein BL1463


BI01235
1021949
1023763
−
conserved hypothetical protein


BI01236
1023782
1024864
−
conserved hypothetical protein


BI01237
1024893
1025600
−
conserved hypothetical protein


BI01238
1025761
1026843
−
possible TraG-related protein


BI01239
1026843
1027799
−
hypothetical protein Blon020262


BI01240
1027799
1028164
−
hypothetical protein Blon020261


BI01242
1028379
1028669
+
hypothetical protein Blon020260


BI01241
1028588
1030942
+
DNA topoisomerase III


BI01243
1030771
1031448
+
hypothetical protein Blon020258


BI01244
1031753
1032193
+
COG1758: DNA-directed RNA polymerase,






subunit K/omega


BI01245
1032161
1032553
−
hypothetical protein Blon020256


BI01246
1032621
1033400
−
Fic protein family family


BI01247
1033518
1034822
+
MC38, putative


BI01248
1034848
1036128
−
PUTATIVE HIPA TRANSCRIPTION






REGULATOR PROTEIN


BI01249
1036128
1036439
−
hypothetical protein Blon020251


BI01250
1036545
1037675
−
conserved hypothetical protein


BI01251
1038618
1040387
−
MC40


BI01252
1040507
1041145
−
conserved hypothetical protein


BI01253
1041250
1042281
−
conserved hypothetical protein


BI01254
1042389
1042865
−
conserved hypothetical protein


BI01255
1043244
1044842
−
ATP binding protein-like protein


BI01256
1044857
1046341
−
conserved hypothetical protein


BI01257
1046369
1048195
−
lipoprotein, putative


BI01258
1048370
1048669
−
conserved hypothetical protein


BI01259
1048710
1049189
−
MC47, putative


BI01713t
1049183
1050538
+
hypothetical protein BL1487


BI01260
1049206
1050405
−
hypothetical protein


BI01261
1050435
1051070
−
hypothetical protein Blon020236


BI01262
1051396
1056213
−
hypothetical COG2217: Cation transport ATPase


BI01263
1056508
1057458
−
hypothetical protein Blon020231


BI01264
1057844
1058440
−
hypothetical COG1192: ATPases involved in






chromosome partitioning


BI01265
1059167
1059430
−
COG1192: ATPases involved in chromosome






partitioning


BI01266
1059569
1060042
−
possible WhiB-like transcription factor


BI01267
1060036
1061400
−
conserved hypothetical protein


BI01727t
1061400
1061597
−
hypothetical protein Blon020220


BI01268
1061748
1061894
−
hypothetical protein


BI01730t
1061882
1062055
−
hypothetical protein Blon020217


BI01269
1062779
1062997
−
conserved hypothetical protein


BI01270
1063127
1063546
+
Helix-turn-helix domain protein


BI01733t
1064092
1064778
+
conserved hypothetical protein


BI01271
1064862
1066490
−
lipoprotein, putative


BI01272
1066742
1067959
−
isocitrate dehydrogenase, NADP-dependent


BI01273
1068051
1069208
+
IMP dehydrogenase family protein


BI01274
1069373
1069861
+
hypothetical protein Blon020211


BI01275
1069955
1072039
+
long-chain-fatty-acid--CoA ligase, putative


BI01276
1072049
1072534
+
polypeptide deformylase


BI01277
1072876
1073736
+
ribosomal protein S2


BI01278
1073818
1074666
+
translation elongation factor Ts


BI01279
1074978
1075580
+
uridylate kinase


BI01280
1075660
1076208
+
ribosome recycling factor


BI01281
1076309
1077217
+
phosphatidate cytidylyltransferase


BI01282
1077557
1078597
+
radical SAM enzyme, Cfr family


BI01283
1078604
1079149
−
protease I


BI01284
1079324
1080091
+
imidazoleglycerol phosphate synthase, cyclase






subunit


BI01285
1080228
1080620
+
phosphoribosyl-AMP cyclohydrolase


BI01286
1080704
1082257
+
anthranilate synthase component I


BI01287
1082328
1082564
−
conserved hypothetical protein


BI01288
1082576
1084174
+
ATP binding protein of ABC transporter


BI01289
1084221
1084925
+
oxidoreductase, short-chain






dehydrogenase/reductase family, putative


BI01290
1084999
1085364
+
narrowly conserved protein with unknown






function


BI01291
1085423
1086091
−
conserved hypothetical protein


BI01292
1086091
1087701
−
ABC transporter, ATP-binding protein


BI01293
1087704
1088600
−
possible ABC transporter permease for cobalt


BI01294
1088405
1089049
−
narrowly conserved protein with unknown






function


BI01295
1089261
1090877
+
conserved hypothetical protein


BI01296
1090916
1091548
+
conserved hypothetical protein


BI01297
1091551
1095093
+
hypothetical myosin-like protein with unknown






function


BI01298
1095170
1096351
+
conserved hypothetical protein


BI01299
1096680
1097084
+
hypothetical protein BL0701


BI01300
1097367
1100384
+
excinuclease ABC, A subunit


BI01301
1100532
1102895
+
excinuclease ABC, C subunit


BI01302
1103007
1103975
+
aroE


BI01303
1103978
1104961
+
Predicted P-loop-containing kinase


BI01304
1105247
1106110
+
Uncharacterized BCR, COG1481


BI01305
1106282
1107484
+
phosphoglycerate kinase


BI01306
1107546
1108346
+
triosephosphate isomerase


BI01307
1108365
1108658
+
preprotein translocase, SecG subunit


BI01308
1108763
1109710
+
L-lactate dehydrogenase


BI01309
1109710
1110558
+
Cof family protein


BI01310
1110672
1112225
+
aminotransferase, class I


BI01311
1112360
1113466
−
membrane protein, putative


BI01312
1113642
1114943
−
branched-chain amino acid transport system II






carrier protein


BI01313
1115108
1116208
−
transaldolase


BI01314
1116332
1118392
−
transketolase


BI01315
1118812
1119927
+
heat-inducible transcription repressor HrcA


BI01316
1119986
1121128
+
dnaJ protein


BI01317
1121180
1121968
−
COG3001: Uncharacterized BCR


BI01318
1122113
1122994
+
undecaprenol kinase, putative


BI01319
1123157
1124146
−
conserved hypothetical protein


BI01320
1124807
1126837
+
threonyl-tRNA synthetase


BI01321
1127061
1127561
+
HIT family protein


BI01322
1127703
1128455
+
conserved hypothetical protein TIGR01033


BI01323
1128464
1129045
+
crossover junction endodeoxyribonuclease RuvC


BI01324
1129106
1129729
+
Holliday junction DNA helicase RuvA


BI01325
1129732
1130793
+
Holliday junction DNA helicase RuvB


BI01326
1130876
1131292
+
preprotein translocase, YajC subunit


BI01327
1131359
1131937
+
adenine phosphoribosyltransferase


BI01328
1132037
1133236
+
succinyl-CoA synthetase, beta subunit


BI01329
1133239
1134147
+
succinyl-CoA synthase, alpha subunit


BI01330
1133954
1135546
+
membrane protein, putative


BI01331
1135497
1137131
+
phosphoribosylaminoimidazolecarboxamide






formyltransferase/IMP cyclohydrolase


BI01332
1137280
1137579
+
hypothetical protein


BI01333
1137484
1138449
−
aquaporin Z, putative


BI01334
1138645
1139412
+
ribosomal large subunit pseudouridine synthase B


BI01335
1139514
1141538
+
possible GTP-binding protein


BI01336
1141896
1143422
+
UDP-glucose pyrophosphorylase


BI01337
1143565
1145475
+
conserved hypothetical protein


BI01338
1145489
1145803
+
hypothetical protein Blon020144


BI01339
1145819
1148407
+
helY


BI01340
1148524
1148868
+
conserved hypothetical protein


BI01341
1149001
1149717
+
hydrolase, haloacid dehalogenase-like family


BI01833t
1149744
1149995
+
conserved hypothetical protein


BI01342
1150135
1150497
−
hypothetical protein Blon020140


BI01343
1150673
1151302
−
COG0789: Predicted transcriptional regulators


BI01344
1151406
1151846
−
possible signal transduction protein


BI01345
1151856
1152596
−
conserved hypothetical protein


BI01346
1152693
1153022
−
small basic protein


BI01347
1153025
1153999
−
conserved hypothetical protein


BI01348
1153992
1154684
−
CDP-diacylglycerol--glycerol-3-phosphate 3-






phosphatidyltransferase, putative


BI01349
1154623
1155471
−
ATP phosphoribosyltransferase


BI01350
1155486
1155746
−
phosphoribosyl-ATP pyrophosphohydrolase


BI01351
1155812
1156477
−
ribulose-phosphate 3-epimerase


BI01352
1156556
1157500
−
prolipoprotein diacylglyceryl transferase


BI01353
1157614
1158480
−
tryptophan synthase, alpha subunit


BI01354
1158507
1160591
−
tryptophan synthase, beta subunit


BI01355
1161120
1161968
−
endonuclease IV


BI00066g
1161414
1162400
+
amino acid permease


BI01356
1162340
1162834
+
amino acid permease


BI01357
1162503
1162667
+
amino acid permease


BI01358
1163206
1164216
−
hypothetical membrane protein with unknown






function


BI01359
1164333
1164536
−
hypothetical protein


BI01360
1164570
1164860
−
abortive infection protein AbiGI, putative


BI01361
1164981
1165262
+
hypothetical protein


BI01362
1165260
1165715
−
lin2984


BI01363
1165903
1166406
+
acetyltransferase, GNAT family, putative


BI01364
1166567
1166746
+
lin0863


BI01365
1166793
1167323
−
acetyltransferase, GNAT family


BI01366
1167392
1167961
−
acetyltransferase, GNAT family


BI01367
1168315
1168992
−
hypothetical protein


BI01368
1169017
1169823
−
hypothetical protein


BI01369
1169832
1170527
−
ABC transporter, ATP-binding protein


BI01370
1170352
1171263
+
hypothetical Response regulator receiver domain


BI01371
1171317
1172225
+
hypothetical protein


BI01372
1172194
1172631
−
hypothetical Integral membrane protein


BI01373
1172956
1173576
−
hypothetical protein


BI01374
1173576
1174301
−
hypothetical protein


BI01873t
1174309
1174962
−
bacteriocin ABC transporter, ATP-binding






protein, putative


BI01375
1175274
1176518
+
IS30 family, transposase [imported]


BI01376
1176714
1177379
−
DNA-binding response regulator


BI01377
1177379
1179001
−
hypothetical ATPase, histidine kinase-, DNA






gyrase B-, and HSP90-like domain protein


BI01378
1179039
1179881
−
hypothetical permease, putative


BI01379
1180057
1180956
−
ABC transporter, ATP-binding protein


BI01380
1181077
1181259
+
hypothetical protein


BI01381
1181154
1181684
−
hypothetical protein


BI01382
1182016
1182315
+
BlsA


BI01383
1182321
1182662
+
hypothetical protein


BI01384
1182847
1183050
−
hypothetical protein


BI01385
1183324
1183446
+
hypothetical protein BL0771


BI01386
1183489
1183932
+
hypothetical protein Blon020116


BI01387
1183955
1184314
−
COG0388: Predicted amidohydrolase


BI01388
1184376
1184531
−
hypothetical protein


BI01389
1184840
1185853
−
inner membrane protein, 60 kDa VC0004






[imported]


BI01390
1186097
1186555
−
hypothetical protein


BI01391
1186942
1187067
+
hypothetical protein


BI01392
1187122
1188783
+
amino acid permease


BI01393
1188993
1189640
−
Signal peptidase I


BI00067g
1189800
1190303
+
conserved hypothetical protein


BI01394
1189721
1190146
−
hypothetical protein Blon020104


BI01395
1190467
1191420
+
lin0466


BI01396
1191479
1191799
+
narrowly conserved hypothetical protein


BI01397
1191887
1192165
+
narrowly conserved hypothetical protein


BI01398
1192540
1193727
+
Unknown, putative


BI01399
1193770
1195530
+
YjeF family protein, putative


BI01400
1195635
1196261
+
possible alpha beta hydrolase


BI01401
1196417
1197286
+
transcriptional regulator, LysR family


BI01402
1197447
1198565
−
conserved hypothetical protein


BI01403
1198783
1198932
−
hypothetical protein


BI01404
1199044
1199736
−
orotate phosphoribosyltransferase


BI01405
1199748
1200716
−
dihydroorotate dehydrogenase


BI01406
1200722
1201543
−
dihydroorotate dehydrogenase, electron transfer






subunit


BI01407
1201682
1202632
−
orotidine 5′-phosphate decarboxylase


BI01408
1202653
1203939
−
dihydroorotase


BI01921t
1204146
1204562
−
Aspartate carbamoyltransferase regulatory chain,






allosteric domain


BI01409
1204565
1205524
−
aspartate carbamoyltransferase


BI01410
1205669
1208896
−
glutamate-ammonia ligase adenylyltransferase






family


BI01411
1208955
1209905
−
EF0040


BI01412
1210042
1210893
−
5,10-methylenetetrahydrofolate reductase


BI01413
1210955
1213255
−
5-methyltetrahydropteroyltriglutamate--






homocysteine S-methyltransferase


BI01414
1213369
1213923
−
phosphohistidine phosphatase SixA, putative


BI01415
1214024
1215091
−
conserved hypothetical protein


BI01416
1215168
1215803
+
serine esterase, putative


BI01417
1215850
1216806
−
oxidoreductase, aldo/keto reductase 2 family


BI01418
1217063
1217995
+
lipC, putative


BI01419
1218234
1219178
+
hypothetical oxidoreductase, zinc-binding






dehydrogenase family


BI01420
1219340
1219642
−
probable ATP binding protein of ABC transporter


BI01421
1220459
1221484
+
transposase (25) BH3998 [imported], putative


BI00069g
1221277
1221948
+
hypothetical protein


BI01422
1221948
1222706
+
Tpase2


BI01423
1222896
1223972
+
hypothetical protein


BI01424
1224236
1224811
+
hypothetical protein


BI01425
1224888
1225190
−
transcriptional regulator, HTH_3 family


BI01426
1225221
1226144
−
hypothetical protein


BI01427
1226238
1227140
−
hypothetical protein


BI01428
1227158
1228765
−
hypothetical protein


BI01429
1229279
1230097
−
hypothetical ADP-ribosylglycohydrolase


BI01430
1231271
1231726
−
hypothetical protein


BI01431
1232085
1232906
+
conserved hypothetical protein


BI01432
1233000
1233539
−
bcp


BI01433
1233681
1234511
−
probable amidase [imported]


BI01434
1234511
1235365
−
hydrolase, haloacid dehalogenase-like family,






putative


BI01435
1235520
1236365
−
amino acid transport protein


BI01436
1236462
1237709
−
possible glycosyltransferase


BI01437
1237841
1238302
−
conserved hypothetical protein


BI01438
1238382
1239917
−
gltD


BI01439
1239922
1244265
−
Conserved region in glutamate synthase family


BI01440
1244835
1245116
+
transcription regulator, LacI family [imported]


BI01441
1245175
1246197
−
conserved hypothetical protein


BI01442
1246656
1246979
+
conserved hypothetical protein


BI01443
1247042
1247227
−
hypothetical protein


BI01444
1247493
1248536
−
transcriptional regulator, LacI family, putative


BI01445
1249246
1250073
+
conserved hypothetical protein


BI01446
1250275
1250571
−
hypothetical protein


BI00071g
1250541
1250888
−
conserved hypothetical protein


BI01447
1250658
1250807
+
hypothetical protein


BI01448
1251252
1252538
+
MATE efflux family protein, putative


BI01449
1252678
1252794
−
hypothetical protein


BI01450
1253083
1254216
+
IS30 family, transposase [imported]


BI01451
1254323
1255327
−
glycerate kinase


BI01452
1255679
1256734
+
transcriptional regulator, LacI family, putative


BI01453
1256820
1258094
−
oxygen-independent coproporphyrinogen III






oxidase, putative


BI01454
1258229
1259890
−
GTP-binding protein LepA


BI01455
1260253
1260510
+
ribosomal protein S20


BI01456
1260768
1261556
−
conserved hypothetical transmembrane protein






with unknown function


BI01457
1261807
1262703
−
transcriptional regulator, MazG family


BI01458
1262903
1264027
−
branched-chain amino acid aminotransferase


BI01459
1264254
1264871
−
ribosomal 5S rRNA E-loop binding protein






Ctc/L25/TL5


BI01460
1265298
1266332
+
conserved hypothetical protein


BI01461
1266474
1267895
−
NAD(P) transhydrogenase, beta subunit






[imported]


BI01462
1267898
1268200
−
NAD(P) transhydrogenase, alpha subunit


BI01463
1268219
1269379
−
NAD(P) transhydrogenase, alpha subunit






[imported]


BI01464
1269798
1271828
+
long-chain-fatty-acid--CoA ligase


BI01465
1271887
1272948
−
GTP-binding protein Era


BI01466
1272953
1274383
−
CBS domain protein


BI01467
1274462
1275052
−
conserved hypothetical protein TIGR00043


BI01468
1275000
1276172
−
PhoH family protein


BI01469
1276194
1276529
−
Hit family protein


BI01470
1276581
1277375
−
conserved hypothetical protein TIGR00046


BI01471
1277619
1278494
+
spoU rRNA methylase family protein


BI01472
1278758
1279939
+
glucose-1-phosphate adenylyltransferase


BI01473
1280035
1280532
−
mrp protein homolog


BI01474
1280635
1281171
−
SUF system FeS assembly protein, NifU family


BI01475
1281201
1282472
−
aminotransferase, class-V


BI01476
1282614
1283390
−
FeS assembly ATPase SufC


BI01477
1283419
1284651
−
FeS assembly protein SufD


BI01478
1284660
1286156
−
FeS assembly protein SufB


BI01479
1286383
1287849
−
conserved hypothetical protein


BI01480
1288225
1289883
−
CTP synthase


BI01481
1290032
1291585
−
dipeptidase, putative


BI01482
1291684
1292127
−
3-dehydroquinate dehydratase, type II


BI01483
1292294
1293835
−
3-dehydroquinate synthase


BI01484
1293999
1295132
−
chorismate synthase


BI01485
1295247
1295717
+
COG0477: Permeases of the major facilitator






superfamily


BI01486
1295891
1297003
−
Uncharacterized BCR, YceG family COG1559


BI01487
1297083
1297535
−
conserved hypothetical protein TIGR00250


BI01488
1297550
1300228
−
alanyl-tRNA synthetase


BI01489
1300359
1300592
−
hypothetical protein Blon020010


BI01490
1300595
1300990
−
conserved hypothetical protein


BI01491
1301196
1301921
−
phosphoglycerate mutase


BI01492
1302158
1304008
+
Acyltransferase family domain protein


BI01493
1304105
1304728
−
ribosomal protein S4


BI01494
1304930
1305895
−
ABC transporter, ATP-binding protein


BI01495
1305900
1307114
−
hypothetical transmembrane protein with






unknown function


BI01496
1307208
1307603
−
conserved hypothetical protein


BI01497
1307751
1310450
−
hypothetical UvrD/REP helicase


BI01498
1310567
1311145
+
xanthine phosphoribosyltransferase


BI01499
1311199
1312560
+
xanthine/uracil permease family protein


BI01500
1312696
1312902
−
transcription regulator, Cro/CI family [imported]-






related protein


BI01501
1312912
1313169
−
hypothetical protein


BI01502
1313326
1314144
−
hydrolase, alpha/beta fold family, putative


BI01503
1314432
1315367
+
conserved hypothetical protein


BI01504
1315462
1315860
−
glyoxalase family protein


BI01505
1316019
1316630
+
isochorismatase


BI01506
1316885
1318360
+
conserved hypothetical protein


BI01507
1318371
1319780
−
membrane protein, putative


BI01508
1319770
1321005
−
membrane protein, putative


BI01509
1321109
1322089
−
daunorubicin resistance ATP-binding protein


BI01510
1322192
1322296
−
hypothetical protein


BI01511
1322475
1323824
+
histidine kinase sensor of two-component system


BI01512
1323917
1324477
+
DNA-binding response regulator


BI01513
1324667
1325287
−
Protein of unknown function subfamily


BI01514
1325308
1326324
−
phosphate transporter family protein


BI01515
1326480
1326674
−
conserved hypothetical protein


BI01516
1326735
1329005
−
carbon starvation protein A


BI01517
1329406
1330668
+
glycosyl hydrolase, family 13, putative


BI01518
1330703
1331404
−
transcriptional regulator, TetR family, putative


BI01519
1331486
1333669
−
possible ATP-dependent RNA helicase


BI01520
1334052
1335338
−
uracil-xanthine permease


BI01521
1335446
1336273
−
phosphoglycerate mutase family domain protein


BI01522
1336327
1336905
−
conserved hypothetical protein


BI01523
1337061
1337612
+
conserved hypothetical protein


BI01524
1337738
1338898
−
conserved hypothetical protein


BI01525
1339275
1340816
−
conserved hypothetical protein


BI01526
1341250
1341687
+
hypothetical COG0653: Preprotein translocase






subunit SecA (ATPase, RNA helicase)


BI01527
1341752
1343449
+
Protein kinase domain protein


BI01528
1343493
1344980
−
permease, putative


BI01529
1345295
1347565
−
drug resistance transporter, EmrB/QacA






subfamily


BI01530
1347576
1347776
−
hypothetical protein


BI01531
1347947
1348309
+
hypothetical Domain of unknown function






(DUF307)


BI01532
1348405
1349910
−
hypothetical protein


BI01533
1349906
1351072
−
hypothetical protein


BI01534
1351166
1351474
−
hypothetical protein


BI02085t
1351280
1351477
+
hypothetical protein Blon021394


BI01535
1351807
1352478
+
COG4186: Predicted phosphoesterase or






phosphohydrolase


BI01536
1352565
1354004
+
conserved hypothetical protein


BI01537
1354044
1354253
+
hypothetical protein BL0925


BI01538
1354253
1354612
+
hypothetical protein BL0925


BI01539
1354729
1355193
+
hypothetical protein


BI01540
1355496
1356380
−
hypothetical protein


BI01541
1356380
1357450
−
hypothetical Phage integrase family


BI01542
1357650
1358675
+
transposase (25) BH3998 [imported], putative


BI00076g
1358468
1359139
+
hypothetical protein


BI01543
1359139
1359897
+
Tpase2


BI01544
1360305
1361546
−
GTP-binding protein YchF


BI01545
1361533
1362351
−
pyrroline-5-carboxylate reductase


BI01546
1362416
1363891
−
proline iminopeptidase


BI01547
1363977
1366433
+
histidine kinase sensor of two-component system


BI01548
1366551
1367345
+
DNA-binding response regulator


BI01549
1367384
1370233
−
possible transport protein


BI01550
1370265
1371176
−
ABC transporter, ATP-binding protein


BI01551
1371528
1372841
−
O-acetylhomoserine sulfhydrylase


BI01552
1373315
1374184
+
pyridoxal kinase, putative


BI01553
1374424
1374924
+
conserved hypothetical protein TIGR00252


BI01554
1374983
1376515
+
Mg chelatase-related protein


BI01555
1376515
1378212
+
DNA processing protein DprA, putative


BI01556
1378272
1380134
+
sdhA


BI01557
1380233
1381195
+
sdhB


BI01558
1381277
1381954
+
probable methyltransferase


BI01559
1382006
1382944
−
conserved hypothetical protein TIGR00730


BI01560
1383180
1384595
−
Na+/H+ antiporter [imported]


BI01561
1385070
1386485
−
ATP-dependent Clp protease, ATP-binding






subunit ClpX


BI01562
1386610
1387308
−
ATP-dependent Clp protease, proteolytic subunit






ClpP


BI01563
1387317
1387907
−
ATP-dependent Clp protease, proteolytic subunit






ClpP


BI01564
1388046
1388423
−
hypothetical protein Blon021418


BI01565
1388538
1390001
−
voltage-gated chloride channel family protein,






putative


BI01566
1390189
1391565
−
trigger factor


BI01567
1391623
1392921
−
3-5 exonuclease domain protein


BI01568
1392921
1393730
−
COG0477: Permeases of the major facilitator






superfamily


BI01569
1393622
1394500
−
pyruvate formate-lyase 1 activating enzyme


BI01570
1394613
1396985
−
formate acetyltransferase


BI01571
1397254
1397475
−
conserved hypothetical protein


BI01572
1397531
1399093
−
NH(3)-dependent NAD+ synthetase


BI01573
1399577
1400725
−
Peptidase, M20/M25/M40 family


BI01574
1400817
1401500
−
permease protein of ABC transporter system


BI01575
1401500
1402702
−
ABC transporter, ATP-binding protein


BI01576
1402839
1403816
−
lipoprotein, YaeC family


BI01577
1404020
1404847
+
hydrolase, haloacid dehalogenase-like family


BI01578
1404975
1407449
−
D-xylulose 5-phosphate/D-fructose 6-phosphate






phosphoketolase


BI01579
1407895
1409454
+
GMP synthase


BI01580
1409723
1410304
+
COG0798: Arsenite efflux pump ACR3 and






related permeases


BI01581
1410343
1410720
+
arsenical resistance protein/arsenate reductase


BI01582
1411265
1411771
+
hypothetical Transposase IS66 family


BI00078g
1411579
1412214
+
hypothetical protein Blon021471


BI01583
1412111
1413136
+
transposase (25) BH3998 [imported], putative


BI00079g
1412929
1413600
+
hypothetical protein


BI01584
1413600
1414358
+
Tpase2


BI01585
1414423
1414911
+
hypothetical COG3436: Transposase and






inactivated derivatives


BI02159t
1415037
1416323
−
COG0477: Permeases of the major facilitator






superfamily


BI01586
1416510
1417160
+
putative ATP-binding protein


BI01587
1417164
1418444
+
Uncharacterized conserved protein


BI01588
1418440
1418820
+
hypothetical protein Blon021466


BI01589
1418965
1420548
+
conserved hypothetical protein


BI01590
1420796
1422598
+
acyltransferase, putative


BI01591
1422687
1423706
+
prsA


BI01592
1423991
1425370
+
UDP-N-acetylglucosamine pyrophosphorylase


BI01593
1425377
1425787
+
iojap-related protein


BI01594
1425942
1426637
+
phosphoglycerate mutase, putative


BI01595
1427363
1428961
+
phosphate acetyltransferase


BI01596
1429099
1429695
+
acetate kinase


BI01597
1429811
1430326
+
hypothetical COG0282: Acetate kinase


BI01598
1430503
1431867
−
3-phosphoshikimate 1-carboxyvinyltransferase


BI01599
1431867
1433036
−
membrane protein, putative


BI01600
1433757
1434125
−
hypothetical COG2217: Cation transport ATPase


BI01601
1434688
1436172
−
galactoside symporter


BI01602
1436515
1439583
+
beta-galactosidase, putative


BI01603
1440389
1441246
+
hypothetical protein


BI01604
1441301
1441966
−
hypothetical protein Blon020709


BI01605
1442167
1442559
−
hypothetical protein


BI01606
1442574
1442990
−
hypothetical protein


BI01607
1442990
1444792
−
hypothetical protein


BI01608
1444688
1445566
+
COG3757: Lyzozyme M1 (1,4-beta-N-






acetylmuramidase)


BI01609
1445667
1445948
+
hypothetical protein


BI01610
1446119
1446796
+
hypothetical protein


BI01611
1447212
1448801
+
hypothetical C-5 cytosine-specific DNA






methylase


BI01612
1448804
1449997
−
hypothetical protein Psyc022392


BI01613
1450130
1450393
+
hypothetical protein


BI01614
1450514
1450891
−
hypothetical protein


BI01615
1451253
1452203
−
hypothetical protein


BI01616
1452503
1452802
−
TnpB


BI01617
1452909
1453127
+
IS861, transposase OrfB


BI01618
1453248
1453586
+
putative transposase subunit


BI01619
1455179
1455604
−
cell division protein FtsZ


BI01620
1455752
1459864
−
hypothetical UvrD/REP helicase


BI01621
1459861
1463163
−
COG3857: ATP-dependent nuclease, subunit B


BI01622
1463295
1465877
−
hypothetical DNA polymerase III, alpha subunit


BI01623
1466012
1467055
+
conserved hypothetical protein


BI01624
1467089
1467886
−
narrowly conserved hypothetical membrane






protein


BI01625
1468160
1468507
−
hypothetical protein BL0124


BI01626
1468949
1469908
−
Pseudouridylate synthases, 23S RNA-specific


BI01627
1469911
1470456
−
lipoprotein signal peptidase


BI01628
1470481
1471857
−
conserved hypothetical protein


BI01629
1472000
1472299
−
COG0762: Predicted integral membrane protein


BI01630
1472424
1472900
−
conserved hypothetical protein


BI01631
1472916
1473830
−
hypothetical Tubulin/FtsZ family, C-terminal






domain


BI01632
1474239
1475480
−
TIM-barrel protein, NifR3 family


BI01633
1475628
1476938
−
glycyl-tRNA synthetase


BI01634
1477533
1478474
+
hydroxyethylthiazole kinase


BI01635
1478743
1481310
+
thiamine biosynthesis protein ThiC


BI01636
1481353
1481679
−
hypothetical protein


BI01637
1481820
1482626
+
phosphomethylpyrimidine kinase


BI01638
1482680
1483054
+
COG0011: Uncharacterized ACR


BI01639
1483563
1484939
+
permease, putative


BI02235t
1485571
1485978
+
conserved hypothetical protein


BI01640
1486039
1487433
+
Serpin (serine protease inhibitor) superfamily


BI01641
1487717
1488517
+
transcriptional regulator, LacI family, putative


BI01642
1488728
1490068
+
sucrose transport protein


BI01643
1490082
1491635
+
sucrose-6-phosphate hydrolase, putative


BI01644
1491833
1492612
+
ABC transporter, permease protein, cysTW






family, putative


BI01645
1492927
1493943
+
pyrimidine precursor biosynthesis enzyme,






putative


BI02246t
1494070
1495254
+
inosine-uridine preferring nucleoside hydrolase


BI01646
1495416
1496207
−
undecaprenyl diphosphate synthase


BI01647
1496207
1496923
−
DNA repair protein RecO


BI01648
1496975
1498684
−
conserved hypothetical protein


BI01649
1498808
1500028
−
1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate






synthase


BI01650
1500028
1501215
−
1-deoxy-D-xylulose 5-phosphate






reductoisomerase


BI01651
1501215
1502915
−
conserved hypothetical protein


BI01652
1503387
1503809
−
conserved hypothetical protein


BI01653
1503919
1504797
−
PDZ domain family protein


BI01654
1505129
1506760
+
conserved hypothetical protein


BI01655
1506836
1508407
−
ATP-dependent DNA helicase PcrA


BI01656
1508553
1510205
+
conserved hypothetical protein


BI01657
1510357
1510578
+
putative ATP-binding protein


BI01658
1510645
1511535
−
PHP domain N-terminal region family


BI01659
1511673
1512407
+
narrowly conserved hypothetical transmembrane






protein


BI01660
1512419
1513309
−
diaminopimelate epimerase


BI01661
1513417
1514208
+
glutamate racemase


BI01662
1514340
1515182
+
Patatin family


BI01663
1515255
1516151
−
Unknown


BI01664
1516314
1516580
−
trans-sulfuration enzyme


BI00087g
1516749
1517024
−
ABC transporter, ATP-binding protein, putative


BI00086g
1517139
1517573
+
conserved hypothetical protein in upf0074


BI01665
1517692
1517940
−
conserved hypothetical protein


BI01666
1518187
1519422
−
cystathionine beta-lyase


BI01667
1519661
1520560
−
glutamine ABC transporter, periplasmic






glutamine-binding protein (glnH)


BI01668
1520629
1521417
−
amino acid ABC transporter, ATP-binding protein


BI01669
1521413
1521952
−
amino acid ABC transporter, permease protein






SP0710 [imported]


BI01670
1522074
1522730
−
amino acid ABC transporter, permease protein


BI01671
1522793
1523605
+
hypothetical Phospholipase/Carboxylesterase


BI01672
1523620
1525872
−
Tn916, tetracycline resistance protein, putative


BI01673
1526091
1526723
+
DNA polymerase III, epsilon subunit


BI01674
1526731
1527318
−
guanylate kinase


BI01675
1527501
1528418
−
orotidine 5′-phosphate decarboxylase, putative


BI01676
1528421
1531801
−
carbamoyl-phosphate synthase, large subunit


BI01677
1531806
1533176
−
carbamoyl-phosphate synthase, small subunit


BI01678
1533219
1533788
−
transcription antitermination factor NusB


BI01679
1533846
1534154
−
Elongation factor P (EF-P)


BI01680
1534514
1535248
+
Unknown, putative


BI01681
1535248
1536033
+
conserved hypothetical protein TIGR00245


BI01682
1536066
1536770
−
Unknown


BI01683
1536878
1539436
−
hypothetical EAL domain


BI01684
1539444
1540751
−
Probable hydrolase transmembrane protein


BI01685
1541332
1543257
+
glycosyltransferase


BI01686
1543387
1543551
−
hypothetical protein


BI01687
1543710
1544600
−
3-hydroxyacyl-CoA dehydrogenase


BI01688
1544959
1546782
−
alpha-xylosidase


BI01689
1546897
1547199
−
hypothetical COG1653: ABC-type sugar transport






system, periplasmic component


BI01690
1547359
1549491
−
possible beta-hexosaminidase A


BI01691
1549605
1550417
−
ABC transporter, permease protein, MalFG






family


BI01692
1551035
1551862
+
conserved hypothetical protein


BI01693
1552142
1553254
−
mrp


BI01694
1553434
1556193
−
DNA ligase, NAD-dependent


BI01695
1556261
1559881
−
conserved hypothetical protein


BI01696
1560102
1562237
+
membrane protein, putative


BI01697
1562555
1564141
+
hypothetical protein Blon021196


BI01698
1564204
1564977
−
ABC transporter, ATP-binding protein, putative


BI01699
1565037
1566299
−
aminotransferase, class I, putative


BI01700
1566573
1567337
−
ROK family protein


BI01701
1567583
1568365
+
Nitroreductase family protein


BI01702
1568413
1569423
−
probable glycosyltransferase


BI01703
1569675
1570325
+
conserved hypothetical protein


BI01704
1570459
1572888
+
ABC transporter, ATP-binding protein, putative


BI01705
1572963
1573265
+
Predicted RNA-binding protein containing KH






domain


BI01706
1573370
1573732
−
conserved hypothetical protein


BI01707
1573842
1574456
+
hypothetical TM2 domain


BI01708
1574885
1575301
+
hypothetical protein Blon021592


BI01709
1575432
1576415
−
D-isomer specific 2-hydroxyacid dehydrogenase






family protein


BI01710
1576714
1578168
+
drug resistance transporter, EmrB/QacA family,






putative


BI01711
1578399
1579418
−
ribose ABC transporter, permease protein






VCA0129 [imported], putative


BI01712
1579418
1580485
−
ribose ABC transporter, permease protein






VCA0129 [imported], putative


BI01713
1580490
1582028
−
ATP binding protein of ABC transporter


BI01714
1582172
1583152
−
ribose ABC transporter, periplasmic D-ribose-






binding protein


BI01715
1583472
1585199
−
lipoprotein, putative


BI01716
1585199
1586752
−
sensor histidine kinase MtrB


BI01717
1586893
1587837
−
hypothetical Response regulator receiver domain


BI01718
1587674
1589005
−
conserved ATP/GTP binding protein


BI01719
1589136
1591535
−
COG0513: Superfamily II DNA and RNA






helicases


BI01720
1591837
1592907
−
Domain of unknown function (DUF344) family


BI02350t
1592976
1593215
−
conserved hypothetical protein


BI01721
1593208
1593801
−
COG0737: 5′-nucleotidase/2′,3′-cyclic






phosphodiesterase and related esterases


BI01722
1593841
1595364
−
hypothetical secreted protein with probable acid






phosphatase domain


BI01723
1595471
1596568
−
glutamine ABC transporter, glutamine-binding






protein/permease protein, putative


BI01724
1596577
1597251
−
glutamine ABC transporter, permease protein


BI01725
1597254
1598090
−
amino acid ABC transporter, amino acid-binding






protein, putative


BI01726
1598125
1598964
−
amino acid ABC transporter, ATP-binding protein


BI01727
1599401
1600468
+
conserved hypothetical protein


BI01728
1600932
1602728
−
aspartyl-tRNA synthetase


BI01729
1602767
1604107
−
histidyl-tRNA synthetase


BI01730
1604264
1605721
+
conserved hypothetical protein


BI01731
1605933
1607723
−
5′-nucleotidase family protein, putative


BI01732
1607898
1608653
−
creatinine amidohydrolase, creatininase


BI01733
1608742
1610115
−
proline/betaine transporter


BI01734
1610158
1610328
+
hypothetical protein


BI01735
1610308
1611378
−
hypothetical protein weakly similar to putative






transcriptional regulator from Streptomyces


BI01736
1611950
1613266
+
N-acyl-D-amino-acid deacylase family protein,






putative


BI01737
1613452
1616058
−
ATP-dependent Clp protease, ATP-binding






subunit ClpC


BI01738
1616208
1617170
+
demannu, putative


BI01739
1617288
1618208
−
hypothetical protein Blon021510


BI01740
1618484
1618870
−
cspB


BI01741
1618943
1620931
−
sensor histidine kinase


BI01742
1620965
1621738
−
DNA-binding response regulator


BI01743
1621689
1622492
−
conserved hypothetical protein


BI01744
1622567
1622854
+
conserved hypothetical protein


BI01745
1622957
1624579
−
chaperone


BI01746
1624820
1625056
−
cold-shock domain family protein


BI01747
1625289
1625870
−
hypothetical protein Blon020592


BI01748
1626163
1626771
+
uracil-DNA glycosylase


BI01749
1626814
1627890
+
ATPase, MoxR family


BI01750
1628022
1628837
+
Protein of unknown function family


BI01751
1628840
1629388
+
conserved hypothetical protein


BI01752
1629388
1630443
+
conserved hypothetical protein


BI01753
1630443
1631471
+
conserved hypothetical protein


BI01754
1631444
1632070
+
platelet binding protein GspB, putative


BI01755
1632316
1632660
+
conserved hypothetical protein


BI01756
1632660
1634261
+
conserved hypothetical protein


BI01757
1634531
1634893
+
conserved hypothetical protein


BI01758
1635034
1635672
−
hypothetical membrane protein with unknown






function


BI01759
1635805
1637238
+
adenylosuccinate lyase VC1126 [imported]


BI01760
1637373
1639931
+
narrowly conserved hypothetical membrane






protein


BI01761
1640080
1640358
+
DNA-binding protein HU


BI01762
1640480
1641937
−
possible DNA-binding protein


BI01763
1641940
1642203
−
hypothetical Protein of unknown function






(DUF797)


BI01764
1642234
1643133
−
possible inositol monophosphatase


BI01765
1643139
1644803
−
hypothetical proteasome-associated protein


BI01766
1644828
1646390
−
cell division control protein 48, AAA family


BI01767
1646454
1647149
−
DedA family protein


BI01768
1647410
1647919
+
phosphoserine phosphatase SerB


BI01769
1648166
1650271
+
primosomal protein N


BI01770
1650333
1651034
+
possible alpha beta hydrolase


BI01771
1651061
1652044
+
methionyl-tRNA formyltransferase


BI01772
1652142
1653908
−
dihydroxy-acid dehydratase


BI01773
1654203
1654484
+
DNA-directed RNA polymerase, omega subunit


BI01774
1654765
1655982
+
S-adenosylmethionine synthetase


BI02420t
1656352
1657425
+
hypothetical protein CV1232









The Open reading frames (ORF) listed in Table 1 are defined by their position in the genomic sequence of SEQ ID No. 1. For example BI00001 is defined by the nucleotide sequence of base numbers 1667321 and 1667608 (inclusive) of SEQ ID No. 1.
EXAMPLES
The following examples further describe and demonstrate embodiments within the scope of the invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention.
Example 1
Isolation of Bifidobacterium Longum Biotype Infantis UCC 35624
Appendices and sections of the large and small intestine of the human G.I.T., obtained during reconstructive surgery, were screened for probiotic bacterial strains. All samples were stored immediately after surgery at −80° C. in sterile containers. Frozen tissues were thawed, weighed and placed in cysteinated (0.05%) one quarter strength Ringers' solution. Each sample was gently shaken to remove loosely adhering microorganisms. Following transfer to a second volume of Ringers' solution, the sample was vortexed for 7 min to remove tightly adhering bacteria. In order to isolate tissue embedded bacteria, samples were also homogenised in a Braun blender. The solutions were serially diluted and spread-plated (100 μl) on to the following agar media: RCM (reinforced clostridial media) and RCM adjusted to pH 5.5 using acetic acid; TPY (trypticase, peptone and yeast extract), Chevalier, P. et al. (1990). MRS (deMann, Rogosa and Sharpe); ROG (acetate medium (SL) of Rogosa); LLA (Liver-lactose agar of Lapiere); BHI (brain heart infusion agar); LBS (Lactobacillus selective agar) and TSAYE (tryptone soya agar supplemented with 0.6% yeast extract). All agar media was supplied by Oxoid Chemicals with the exception of TPY agar. Plates were incubated in anaerobic jars (BBL, Oxoid) using CO2 generating kits (Anaerocult A, Merck) for 2-5 days at 37° C.
Gram positive, catalase negative rod-shaped or bifurcated/pleomorphic bacteria isolates were streaked for purity on to complex non-selective media (TPY). Isolates were routinely cultivated in TPY medium unless otherwise stated at 37° C. under anaerobic conditions. Bifidobacteria species were stocked in 40% glycerol and stored at −20° and −80° C.
Approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their Gram reaction, cell size and morphology, growth at 15° C. and 45° C. and fermentation end-products from glucose. Greater than sixty percent of the isolates tested were Gram positive, homofermentative cocci arranged either in tetrads, chains or bunches. Eighteen percent of the isolates were Gram negative rods and heterofermentative coccobacilli.
The remaining isolates (twenty-two percent) were predominantly homofermentative coccobacilli. Thirty eight strains were characterised in more detail. All thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan.
Bifidobacterium longum biotype infantis strain 35624 was chosen for full genome sequencing from this group of strains due to its proven anti-inflammatory activity in murine models of colitis (McCarthy et. al., 2004) and its immunomodulatory effects following oral consumption by Irritable Bowel Syndrome (IBS) patients (O'Mahony et al., 2005).
Example 2
Sequencing the Genome of Bifidobacterium Longum Infantis 35624
The Bifidobacterium longum biotype infantis strain 35624 genome sequence was determined using a whole shotgun approach. For this purpose two libraries were constructed: a small insert library (insert size ranging between 2 and 4 kb) employing pGEM-T easy vector (Promega) and a large insert (insert size ranging between 40 and 45 kb) cosmid library (Epicentre Technologies). Sequence sampling from these banks generated just over 26,828,618 base pairs of useable sequence data, which represented about 11.9-fold coverage of the Bifidobacterium longum biotype infantis strain 35624 genome (performed by MWG-Biotech, Ebersberg, Germany). Sequence reads were assembled using Phrap (Green) into 11 contigs. Gap closure and quality improvement of the initial sequence assembly was achieved by additional primer-directed sequencing using pre-identified clones from the libraries resulting in a single contig, which represented a circular chromosome of 2,264,374 by long. Based on the final consensus quality scores, we estimate an overall error rate of <1 per 4×105 bases
Example 3
Analysing the Genome of Bifidobacterium Longum Biotype Infantis 35624
Protein-encoding open reading frames (ORFs) were predicted using a combination of the methods Glimmer (Delcher et al., 1999b; Salzberg et al., 1998) and GeneBuilder (Internally developed software), as well as comparative analysis involving BLASTX (Altschul et al., 1997)
Results from the gene finder programs were manually combined, and preliminary identification of ORFs was made on the basis of BLASTP (Altschul et al., 1997) analysis against a non-redundant protein database provided by the National Centre for Biotechnology Information (Wheeler et al., 2005). Artemis (Rutherford et al., 2000), was used to inspect the identified ORFs and its associated BLASTP results. A manual inspection was performed in order to verify or, if necessary, redefine the start and stop of each predicted coding region. Annotation made use of the GC frame plot feature of Artemis, ribosome-binding site information obtained from RBSfinder (Suzek et al., 2001), alignments with similar ORFs from other organisms and G+C content analysis.
Example 4
Identifying Unique Genes in the Genome of Bifidobacterium Longum Infantis 35624
Assignment of protein function to predicted coding regions of the Bifidobacterium longum biotype infantis strain 35624 genome was performed using internally developed software and manual inspection. Primary functional classification of the Bifidobacterium longum biotype infantis strain 35624 gene products was performed according to the Riley rules (Riley, 1998a; Riley, 1993). The COG assignment was performed using XUGNITOR (Tatusov,). HMMER (Eddy,) was used to assign PFAM (Bateman et al., 2002) classification to the predicted proteins. TMHMM (Krogh et al., 2001) was used to predict transmembrane sequences, and SignalP (Bendtsen et al., 2004) was used for the prediction of signal peptides. Ribosomal RNA genes were detected on the basis of BLASTN searches and annotated manually. Transfer RNA genes were identified using tRNAscan-SE (Lowe and Eddy, 1997). Miscellaneous-coding RNAs were identified using the Rfam database (Griffiths-Jones et al., 2005) utilizing the INFERNAL software package (Eddy, 2002). Insertion sequence elements were identified using Repeatfinder (Volfovsky et al., 2001), Reputer (Kurtz & Schleiermcher, 1999) and BLAST (Altschul et al., 1990) and annotated manually. IS families were assigned using ISFinder. Carbohydrate-active enzymes were identified based on similarity to the carbohydrate-active enzyme (CAZy) database entries (Coutinho & Henrissat, 1999), and COG and PFAM classes annotated with carbohydrate enzyme activity. Transporter classification was performed according to the TC-DB scheme (Busch & Saier, 2002).
We identified a region from base numbers 44824 to 472245 (inclusive) of SEQ ID No. 1 that we designated exopolysaccharide (EPS) region 1 (SEQ ID No. 2). The EPS region 1 encodes the following genes:







TABLE 2







Open reading frames of EPS region 1 of the UCC 35624 genome















Protein


Gene ID
Strand
Description
DNA sequence
sequence





BI00778
+
glycosyl transferase CpsE
SEQ. ID No. 93
SEQ. ID No. 133


BI00779
+
COG0840: Methyl-accepting chemotaxis
SEQ. ID No. 94
SEQ. ID No. 134




protein


BI00780
+
possible Etk-like tyrosine kinase involved in
SEQ. ID No. 95
SEQ. ID No. 135




Eps biosynthesis


BI00781
+
hypothetical glycosyl transferase, group 1
SEQ. ID No. 96
SEQ. ID No. 136




family protein


BI00782
+
putative glycosyltransferase protein
SEQ. ID No. 97
SEQ. ID No. 137


BI00783
+
NAD dependent epimerase/dehydratase
SEQ. ID No. 98
SEQ. ID No. 138




family protein


BI00784
+
UDP-glucose 6-dehydrogenase
SEQ. ID No. 99
SEQ. ID No. 139


BI00785
+
hypothetical glycosyl transferase, group 1
SEQ. ID No. 100
SEQ. ID No. 140




family protein


BI00786
+
hypothetical Eps11I
SEQ. ID No. 101
SEQ. ID No. 141


BI00787
+
hypothetical Bacterial transferase
SEQ. ID No. 102
SEQ. ID No. 142




hexapeptide (three repeats)


BI00788
+
hypothetical Capsular polysaccharide
SEQ. ID No. 103
SEQ. ID No. 143




synthesis protein


BI00789
+
hypothetical protein
SEQ. ID No. 104
SEQ. ID No. 144


BI00790
+
Eps9K
SEQ. ID No. 105
SEQ. ID No. 145


BI00791
+
hypothetical Polysaccharide biosynthesis
SEQ. ID No. 106
SEQ. ID No. 146




protein


BI00792
+
hypothetical Bacterial transferase
SEQ. ID No. 107
SEQ. ID No. 147




hexapeptide (three repeats)


BI00793
−
NAD-dependent epimerase/dehydratase
SEQ. ID No. 108
SEQ. ID No. 148




family protein, putative


BI00794
−
transposase, degenerate
SEQ. ID No. 109
SEQ. ID No. 149


BI00795
−
hypothetical COG2963: Transposase and
SEQ. ID No. 110
SEQ. ID No. 150




inactivated derivatives


BI00796
+
dTDP-glucose 4,6-dehydratase
SEQ. ID No. 111
SEQ. ID No. 151


BI00797
+
dTDP-4-dehydrorhamnose 3,5-epimerase
SEQ. ID No. 112
SEQ. ID No. 152


BI00798
+
glucose-1-phosphate thymidylyltransferase
SEQ. ID No. 113
SEQ. ID No. 153









We also identified a region from base numbers 2071426 to 2097099 (inclusive) of SEQ ID No. 1 that we designated EPS region 2 (SEQ ID No. 3). The EPS region 2 encodes the following genes:







TABLE 3







Open reading frames of EPS region 2 of the UCC 35624 genome















Protein


Gene ID
Strand
Description
DNA sequence
sequence





BI00319
+
dTDP-glucose 4,6-dehydratase
SEQ. ID No. 114
SEQ. ID No. 154


BI00320
+
conserved hypothetical protein
SEQ. ID No. 115
SEQ. ID No. 155


BI00321
+
conserved hypothetical protein
SEQ. ID No. 116
SEQ. ID No. 156


BI00423t
+
conserved putative transposase
SEQ. ID No. 117
SEQ. ID No. 157


BI00322
−
IS1533, OrfB
SEQ. ID No. 118
SEQ. ID No. 158


BI00323
−
transposase (25) BH3998 [imported],
SEQ. ID No. 119
SEQ. ID No. 159




putative


BI00324
−
glycosyltransferase, putative
SEQ. ID No. 120
SEQ. ID No. 160


BI00325
−
conserved sialic acid-specific 9-O-
SEQ. ID No. 121
SEQ. ID No. 161




acetylesterase


BI00326
+
hypothetical Acyltransferase family
SEQ. ID No. 122
SEQ. ID No. 162


BI00327
−
conserved > hypothetical membrane protein
SEQ. ID No. 123
SEQ. ID No. 163




with unknown function


BI00328
−
hypothetical Glycosyl transferase family 8
SEQ. ID No. 124
SEQ. ID No. 164


BI00329
−
hypothetical glycosyl transferase, group 2
SEQ. ID No. 125
SEQ. ID No. 165




family protein


BI00330
−
polysaccharide ABC transporter, ATP-
SEQ. ID No. 126
SEQ. ID No. 166




binding protein


BI00331
−
polysaccharide ABC transporter, permease
SEQ. ID No. 127
SEQ. ID No. 167




protein, putative


BI00332
+
hypothetical Glycosyl transferase family 8
SEQ. ID No. 128
SEQ. ID No. 168


BI00333
−
UDP-glucose 6-dehydrogenase
SEQ. ID No. 129
SEQ. ID No. 169


BI00334
+
hypothetical NAD dependent
SEQ. ID No. 130
SEQ. ID No. 170




epimerase/dehydratase family


BI00335
−
membrane protein, putative
SEQ. ID No. 131
SEQ. ID No. 171


BI00336
−
conserved hypothetical protein
SEQ. ID No. 132
SEQ. ID No. 172









Example 5
Isolation and Screening of EPS-producing Bifidobacterial Strain from Fecal Samples
Fecal Sample Preparation
Fecal samples were collected by the subjects using a Kendall precision commode specimen collection system. The collected samples were stored chilled in a cold pack prior to sample processing. Only samples that are less than twenty four hours old were used in the evaluations.
A 10.0 gm sample of mixed fecal material was placed into a plastic stomaching bag containing 90 ml of saline. The suspension was stomached for 2 minutes. The suspension was filtered through a gauze pad contained within a disposable funnel. Following the filtration, 45 ml of the filtered fecal homogenate was transferred to a 50 ml disposable centrifuge tube. This fecal suspension was further used for DNA extraction or for bacterial isolation.
Screening Fecal Samples Using Three TaqMan Real-Time PCR Assays.


    Fecal Sample DNA Preparation. A 2.0 ml aliquot of the fecal homogenate was pelleted using a microcentrifuge. The pellets were resuspended in 20 mg/ml lysozyme, for 2 hours at 37° C. DNA was extracted using a QIAamp DNA Stool Mini Kit (Qiagen). The DNA concentration was measured by Pico Green assay (Molecular Probes). Once the DNA concentration was measured, the DNA was stored at 4° C.
    TaqMan Real-Time PCR Reactions. The test samples were diluted to a concentration of DNA of 2 ng/ul so that 5 μl contained a total of 10 ng DNA. Samples were assayed by a total of three separate assays.

The following reaction mix was made:
















Water
15.75 μl


10 μM forward primer
 1.5 μl (300 nM final concentration)


10 μM reverse primer
 1.5 μl (300 nM final concentration)


10 μM TaqMan probe
   1 μl (200 nM final concentration)


BSA (20 mg/ml)
 0.25 μl (0.1 ug/ml final concentration)


TaqMan Universal Master Mix
  25 μl









A bulk mix was made for the number of samples to be assayed. A 45 μl aliquot was dispensed into each well of a 96 well microtitre plate, then 5 μl DNA was added to each well. The plate was spun briefly, and placed into the thermocycler (ABI 7900 HT). The standard TaqMan thermocycling protocol was used.

    TanMan RT-PCR Program. The standard TaqMan quantitative PCR thermocycling protocol is as follows:


Step 1: 95° C. for 10 minutes (to activate the AmpliTaq Gold polymerase)
Step 2: 95° C. for 15 seconds (the denaturation step)
Step 3: 60° C. for 60 seconds (the priming/polymerization step)
Steps 2 and 3 are repeated 40 times. Fluorescent data is collected at step 3.

    Primers and Probes for Three TaqMan RT-PCR assays. The fecal sample DNAs were screened using a EPS gene-specific assay and two B. infantis 35624 Unknown gene-specific assays (Unknown genes UNK1 and UNK2). The specific genes used and their TaqMan primer sets are shown in Table 4 below.










TABLE 4







UCC 35624 Primer set for TaqMan PCR



















TaqMan



Target


Genome
Genome
Probe


Gene
Name
Sequence 5′-3′
start
end
label





BI01615
UNK1-
CCATGAGCGGTTTCACGAA
1451446
1451428
5′ 6-



(UNK-1)
F1
(SEQ ID No. 4)


FAM 3′



UNK1-
TTGGACGGTGCCTGTGATTA
1451393
1451412
NFQ-



R1
(SEQ ID No. 5)


MG



UNK1-
CGGGCAATCAAC
1451426
1451415



MGB1
(SEQ ID No. 6)


 


BI02420t
UNK2-
ACTTGACGTACCGTTTTGAGATTTC
1656479
1656503
5′ 6-


(UNK-2)
F1
(SEQ ID No. 7)


FAM 3′



UNK2-
CTAAGCATGGCAAGGCTGATAGT
1656562
1656540
NFQ-



R1
(SEQ ID No. 8)


MGB



UNK2-
TGCGACCAACACGC
1656525
1656538



MGB1
(SEQ ID No. 9)


 


BI00783
EPS-F1
GGGTCCAATAAGAAGGTTCCATATT
 456491
 456515
5′ 6-


(EPS)

(SEQ ID No. 10)


FAM 3′



EPS-R1
GCATGTGCCAACAGCTCATC
 456591
 456572
TAMR




(SEQ ID NO. 11)



EPS-
CGGATGACAAGGTAGATAATCCAGTGAGCCTATAC
 456519
 456553



TAMRA
(SEQ ID No. 12)









The fecal samples which showed high DNA concentration by the B. infantis 35624 EPS gene-specific assay, but negative reactions by using B. infantis 35624 Unknown gene-specific assays, were further used for the isolation of potential EPS-producing bacteria.
Example 6
Isolation and Characterization of BL1207 from Fecal Samples
One milliliter of bacterial suspension (see Example 5 above) was transferred to 9.0 ml of sterile phosphate-buffered saline which constituted the 10−1 dilution. One milliliter of this 10−1 dilution was transferred to 9.0 ml of sterile phosphate-buffered saline which was the 10−2 dilution. This process was continued until the 10−10 dilution was prepared. Then, 0.1 ml of each dilution was plated onto the surfaces of Reinforced Clostridial Agar (RCA) plates (BD or equivalent) and Lactobacillus Man-Rogosa Sharpe agar (MRSA) plates (BD or equivalent). The plates were incubated under anaerobic condition (COY anaerobic Chamber) at 33° C.±2° C. for 48-72 hours.
Following incubation, single colonies (a total of approximately 100 colonies) were picked from RCA and MRSA plates and further streaked on new plates for isolate purification. The plates with the streaked colonies were incubated under anaerobic conditions (COY anaerobic Chamber) at 33° C.±2° C. for 48 to 72 hours. After incubation, the pure colonies observed on plates were then submitted for DNA extraction.
Screening Fecal Isolates Using Three TaqMan Real-Time PCR Assays
The bacterial DNA was extracted using the PremanTM Ultra Sample Preparation Reagent and Protocol (Applied Biosystems). The DNA was further analyzed using three TaqMan RT-PCR assays (EPS gene-specific assay [EPS-1] and two B. infantis 35624 Unknown gene-specific assays [UNK1 and UNK2] as described above in Example 5. Only one isolate showed B. infantis 35624 EPS gene-specific assay positive, but B. infantis 35624 Unknown gene-specific assays-negative. This isolate was further identified using 16S rDNA sequencing.
Identification of Potential EPS-producing Strain by 16S rDNA Sequencing.
The 16S rRNA gene fragment was amplified and sequenced using ABI Full Gene PCR kit (Applied Biosystems, Foster City, Calif.).
(1). 16S rRNA Gene Amplification:
PCR amplification was carried out on a GeneAmp PCR System 9700 thermal cycler with the following program:
















Initial Hold:
95° C. for 10 minutes



30Cycles:
95° C. for 30 seconds (Denaturing)




60° C. for 30 seconds (Annealing)




72° C. for 45 seconds (Extension)



Final Extension:
72° C. for 10 minutes










(2). 16S rRNA Gene Sequencing:

Sequencing was further performed on the thermal cycler using the following program:
















25 Cycles:
96° C. for 10 seconds (Denaturing)




50° C. for 5 seconds (Annealing)




60° C. for 4 minutes (Extension)



Final step
Hold at 4° C.










The sequencing PCR product was further purified using DyeEXTM 2.0 spin kit and sequenced using 3130 x1 Genetic Analyzer (Applied Biosystems, Foster City, Calif.).
(3) Sequence Data Analysis:
Comparison of the consensus sequences with GenBank sequences was done by using Basic Local Alignment Search Tool (BLAST). The GenBank search indicated that the B infantis 35624 EPS gene-specific positive, but B. infantis 35624 Unknown gene-specific negative strain is Bifidobacterium longum. This strain is designated BL1207.
Example 7
Isolation and Screening of EPS-Expressing Bifidobacterial Longum Strains
Isolation of Bacterial Strains
Bacteria were isolated from bowel tissue and/or fecal samples using the methodology described in Example 1 above. In particular, Bifidobacterium longum strain AH121a was isolated from feline bowel tissue and Bifidobacterium longum strain AH1714 was isolated from colonic biopsy tissue from healthy human subjects.
EPS Gene Cluster Screen


    Bacterial strains were screened for the presence of genes from EPS cluster 1 (Table 2 above) and EPS cluster 2 (Table 3 above) using the primers listed in Tables 5 and 6 below. Briefly, the following methodology was used for the PCR EPS cluster gene screen:
    10 ml Modified Rogosa broth media (+0.05% cysteine) was inoculated aseptically with a freshly grown colony of the bacterial strain and incubated anaerobically at 37° C. until turbid (about 16 to about 24 hours). The broth cultures were centrifuged and DNA was isolated from the resultant pellet using a SigmaTM extraction procedure. A nanodrop was used to ascertain the concentration of DNA in the sample and samples were diluted using DEPC water to a final concentration of 50 ng/ul DNA per sample. The template DNA samples were used in individual PCR reactions with the primer sets listed in Tables 5 and 6 below under the following conditions:

















Time



Step
Temp (° C.)
(sec)


















1
95
240 



2
95
45


3
60
45


4
72
45
repeat steps 2 to 4, 25 times


5
4
hold









    The primers were specifically designed to amplify a PCR product of approximately 500 base pair for the 40 genes of EPS clusters 1 and 2. PCR products were visualised following agarose gel electrophoresis with an appropriate DNA ladder for reference sizing. The presence (YES) or absence (NO) of a 500 by PCR product is indicated in Tables 7 and 8 below.










TABLE 5







Primers for screening bacterial strains for the presence



of genes from EPS cluster 1













Primer






Gene ID
name
LRFR
Sequence
SEQ ID NO.





BI00778
1.01
L
tat gtt gcc ggc att tat ca
SEQ ID No. 13



 


BI00778
1.01
R
tgc gcg ttc atg tca ata at
SEQ ID No. 14


 


BI00779
1.02
L
ggc gta gca agt tca agg ag
SEQ ID No. 15


 


BI00779
1.02
R
aat aac cgc tgc agg aac ac
SEQ ID No. 16


 


BI00780
1.03
L
gtg cag gac ggt aat gga gt
SEQ ID No. 17


 


BI00780
1.03
R
gct tcg ggt ctg gat cat ta
SEQ ID No. 18


 


BI00781
1.04
L
tgc tga caa gtg gag tct gg
SEQ ID No. 19


 


BI00781
1.04
R
cca cgt cta cga gca act ca
SEQ ID No. 20


 


BI00782
1.05
L
gaa agc gaa gag tgg tct gg
SEQ ID No. 21


 


BI00782
1.05
R
ccg gct gat ttg atg aga tt
SEQ ID No. 22


 


BI00783
1.06
L
tgc cgc tgt act ggt cac
SEQ ID No. 23


 


BI00783
1.06
R
gca tgt gcc aac agc tca
SEQ ID No. 24


 


BI00784
1.07
L
cca aca cgt atc tgg cac tg
SEQ ID No. 25


 


BI00784
1.07
R
tcg gag cca aag aag gta ga
SEQ ID No. 26


 


BI00785
1.08
L
ata ccg cgt atg ctt tgg ac
SEQ ID No. 27


 


BI00785
1.08
R
aaa cgg taa cca ctc gct tg
SEQ ID No. 28


 


BI00786
1.09
L
atg gga tcg atg cat gaa at
SEQ ID No. 29


 


BI00786
1.09
R
ttc tcg gca ata aac cgt tc
SEQ ID No. 30


 


BI00787
1.10
L
cca gcg gtt att tcg ttg tt
SEQ ID No. 31


 


BI00787
1.10
R
ggt ggc atg atc ctt atg ct
SEQ ID No. 32


 


BI00788
1.11
L
gct atc ttc acc gca ttg gt
SEQ ID No. 33


 


BI00788
1.11
R
cca gtc agg gaa ggt cac at
SEQ ID No. 34


 


BI00789
1.12
L
tga aat aca cgc aac ccg ta
SEQ ID No. 35


 


BI00789
1.12
R
aatgcgtcaaaaccgatacc
SEQ ID No. 36


 


BI00790
1.13
L
gga aag caa tga gga agc tg
SEQ ID No. 37


 


BI00790
1.13
R
gat ttg atg caa agc aag ca
SEQ ID No. 38


 


BI00791
1.14
L
gtg agt acc gtt tcc gca at
SEQ ID No. 39


 


BI00791
1.14
R
ttc ctt ggt tcc cgt gat ag
SEQ ID No. 40


 


BI00792
1.15
L
gct ggg att ttg gaa gtg aa
SEQ ID No. 41


 


BI00792
1.15
R
tgt tac ccc cgg cat aat aa
SEQ ID No. 42


 


BI00793
1.16
L
acc ggt aac gtt cag att gc
SEQ ID No. 43


 


BI00793
1.16
R
gca ata ccg cct tga cct ta
SEQ ID No. 44


 


BI00794
1.17
L
ttg tac cac cac acg tac cg
SEQ ID No. 45


 


BI00794
1.17
R
cgc gag ttc aat ggc tat g
SEQ ID No. 46


 


BI00795
1.18
L
aca tcg acc tcc atc tcc ag
SEQ ID No. 47


 


BI00795
1.18
R
ata cgt aac agc ggc tcc ac
SEQ ID No. 48


 


BI00796
1.19
L
aag tac gat gtg cgc tac ca
SEQ ID No. 49


 


BI00796
1.19
R
cat cac ggt cag gat gtc ac
SEQ ID No. 50


 


BI00797
1.20
L
cga ata cac gga cat caa cg
SEQ ID No. 51


 


BI00797
1.20
R
gag aat cga gca gct gga ac
SEQ ID No. 52


 


BI00798
1.21
L
tgg gag agg agt tca tcg ac
SEQ ID No. 53


 


BI00798
1.21
R
gta tcc agc cat gcg taa cc
SEQ ID No. 54

















TABLE 6







Primers for screening bacterial strains for the presence



of genes from EPS cluster 2













Primer






Gene ID
name
LRFR
Sequence
SEQ ID NO.





BI00319
2.01
L
acg gac tca aaa cca cca tc
SEQ ID No. 55



 


BI00319
2.01
R
acc ctg ctt ccg gta ctt tt
SEQ ID No. 56


 


BI00320
2.02
L
gcc tac gca aga cct tat gc
SEQ ID No. 57


 


BI00320
2.02
R
cgt tat acg cgt gct tga ga
SEQ ID No. 58


 


BI00321
2.03
L
tgg aac gca ata ttc aac ga
SEQ ID No. 59


 


BI00321
2.03
R
cca agt atg gct cca cga at
SEQ ID No. 60


 


BI00423t
2.04
L
acg cct gtc tat ggt tgg aa
SEQ ID No. 61


 


BI00423t
2.04
R
cgg tag gac tcg ttc tcg tc
SEQ ID No. 62


 


BI00322
2.05
L
tcg agg ttc gag gtg aag at
SEQ ID No. 63


 


BI00322
2.05
R
cct gtt cga gaa gga gaa cg
SEQ ID No. 64


 


BI00323
2.06
L
atg gaa gca tgt ggt cct tc
SEQ ID No. 65


 


BI00323
2.06
R
att tcc tgg tgg tgt cgt tc
SEQ ID No. 66


 


BI00324
2.07
L
atg gcg aaa ctg ttg gac tc
SEQ ID No. 67


 


BI00324
2.07
R
gct acc gtg cct tct cat tc
SEQ ID No. 68


 


BI00325
2.08
L
gcc gaa tcg ctt ttg aaa ta
SEQ ID No. 69


 


BI00325
2.08
R
aaa tcc tca tcg ggg aaa ac
SEQ ID No. 70


 


BI00326
2.09
L
gtt tat ttt cgc cgt gcc ta
SEQ ID No. 71


 


BI00326
2.09
R
aat tcc aat ggc ttt tgc tg
SEQ ID No. 72


 


BI00327
2.10
L
atg tgc gaa tcc gac ata ca
SEQ ID No. 73


 


BI00327
2.10
R
tgc tta tct cgt ccc cat tc
SEQ ID No. 74


 


BI00328
2.11
L
gca aaa tgc ttg gct tct tc
SEQ ID No. 75


 


BI00328
2.11
R
ctg gat tcc gat gat gct tt
SEQ ID No. 76


 


BI00329
2.12
L
ctg cac gta tcg gga ttt tt
SEQ ID No. 77


 


BI00329
2.12
R
ctc ggc aga gga cag gat ag
SEQ ID No. 78


 


BI00330
2.13
L
gat cat cga cac gca atg ac
SEQ ID No. 79


 


BI00330
2.13
R
taa ggc cat cct cat caa gg
SEQ ID No. 80


 


BI00331
2.14
L
tct ggg gaa agc agg tta tg
SEQ ID No. 81


 


BI00331
2.14
R
ctg tgc ggt acc tgt ttg tg
SEQ ID No. 82


 


BI00332
2.15
L
aat tac gtc ccg atg ctc ac
SEQ ID No. 83


 


BI00332
2.15
R
caa tac acc ggc ttg gaa gt
SEQ ID No. 84


 


BI00333
2.16
L
tgt aga cct tgt cgc tca cg
SEQ ID No. 85


 


BI00333
2.16
R
gca tcg gtg acg gct ata at
SEQ ID No. 86


 


BI00334
2.17
L
gtg ctc gac aag ctg acg ta
SEQ ID No. 87


 


BI00334
2.17
R
gtg ttc cgc ata cca atc g
SEQ ID No. 88


 


BI00335
2.18
L
ggc gag tgc acc aaa taa at
SEQ ID No. 89


 


BI00335
2.18
R
cga ttc cgt cta ttg gtt cg
SEQ ID No. 90


 


BI00336
2.19
L
ata agt ccg gtg gca atc ag
SEQ ID No. 91


 


BI00336
2.19
R
caa tgg atg ata cgg tgc tg
SEQ ID No. 92
















TABLE 7







Results of EPS cluster 1 gene screen














B. longum
B. longum
B. longum
B. longum


Gene ID
Primer set
35624
1207
AH121A
1714





BI00778
1.01
YES
YES
NO
YES


BI00779
1.02
YES
YES
NO
YES


BI00780
1.03
YES
YES
NO
YES


BI00781
1.04
YES
YES
YES
YES


BI00782
1.05
YES
YES
YES
YES


BI00783
1.06
YES
YES
YES
YES


BI00784
1.07
YES
YES
YES
YES


BI00785
1.08
YES
YES
YES
YES


BI00786
1.09
YES
YES
YES
YES


BI00787
1.10
YES
YES
YES
YES


BI00788
1.11
YES
YES
YES
NO


BI00789
1.12
YES
YES
YES
YES


BI00790
1.13
YES
YES
YES
YES


BI00791
1.14
YES
YES
YES
YES


BI00792
1.15
YES
YES
YES
YES


BI00793
1.16
YES
YES
NO
YES


BI00794
1.17
YES
YES
NO
YES


BI00795
1.18
YES
YES
NO
YES


BI00796
1.19
YES
YES
YES
YES


BI00797
1.20
YES
NO
NO
NO


BI00798
1.21
YES
YES
YES
YES





In which YES indicates the presence and NO indiates the absence of a 500 bp PCR product.













TABLE 8







Results of EPS cluster 1 gene screen














B. longum
B. longum
B. longum
B. longum


Gene ID
Primer set
35624
1207
AH121A
1714





BI00319
2.01
YES
NO
NO
NO


BI00320
2.02
YES
NO
NO
NO


BI00321
2.03
YES
NO
NO
NO


BI00423t
2.04
YES
NO
NO
NO


BI00322
2.05
YES
NO
NO
NO


BI00323
2.06
YES
NO
NO
NO


BI00324
2.07
YES
NO
NO
NO


BI00325
2.08
YES
NO
NO
NO


BI00326
2.09
YES
NO
NO
NO


BI00327
2.10
YES
NO
NO
NO


BI00328
2.11
YES
NO
NO
NO


BI00329
2.12
YES
NO
NO
NO


BI00330
2.13
YES
NO
NO
NO


BI00331
2.14
YES
NO
NO
NO


BI00332
2.15
YES
NO
NO
NO


BI00333
2.16
YES
NO
NO
NO


BI00334
2.17
YES
NO
NO
NO


BI00335
2.18
YES
YES
NO
YES


BI00336
2.19
YES
YES
YES
YES





In which YES indicates the presence and NO indiates the absence of a 500 bp PCR product.






Congo Red Agar Screen

    A Congo red agar screen was used to phenotypically screen for EPS expressing bacterial strains. Briefly, 10 ml Modified Rogosa broth media (+0.05% cysteine) was inoculated aseptically with a freshly grown colony of the bacterial strain and incubated anaerobically at 37° C. until turbid (about 16 to about 24 hours). The broth cultures were aseptically streaked onto Congo Red Agar plates and incubated anaerobically at 37° C. for 48 hours. It is believed that EPS produced as a by-product of the growth and/or metabolism of certain strains prevents the uptake of the Congo red stain resulting in a cream/white colony morphology. Stains that produce less EPS take up the Congo red stain easily, resulting in a pink/red colony morphology. Strains that do not produce an EPS stain red and look almost transparent in the red agar background.
    Referring to FIGS. 6 to 12, the following colony morphologies were observed:









TABLE 9







Colony morphologies from Congo red agar screen








Bacterial Strain
Colony morphology





B. longum 35624 (FIG. 6)
Convex, mucoid, bright white colonies


B. longum AH121A (FIG. 7)
Convex, mucoid, bright white colonies


B. logum AH1714 (FIG. 8)
Convex, mucoid, bright white colonies


B. longum AH0119 (FIG. 9)
Convex, mucoid, pale pink/off white



colonies


B. breve UCC2003 (FIG. 10)
Convex, mucoid, pale pink/off white



colonies


L. rhamnosus AH308 (FIG. 11)
Flat, semi-mucoid, pale pink/off white



colonies


L. salivarius UCC1 (FIG. 12)
Flat, non-mucoid, clear/transparent



colonies









Example 8
B. infantis 35624 and BL1207 Induce Nearly Identical Cytokine Profiles in PBMCs
Peripheral blood mononuclear cells (PBMCs) were isolated from fresh human peripheral blood using BD Vacutainer CPT tubes (BD catalog 362761), as per the manufacturer's instructions. PBMCs were washed and resuspended in Dulbecco's MEM (Gibco catalog 10569-010) plus 25 mM HEPES, 10% fetal bovine serum (Sigma catalog F4135), and 1% penicillin/streptomycin (Sigma catalog P0781). 2×105 PBMCs (in 200 μl of DMEM) were plated into each well of a 96-well culture plate.
Bacteria were grown in Difco MRS media and harvested just after entering into stationary phase. All cells were grown under anaerobic conditions at 37° C. Growth curves (OD vs # of live cells) were constructed for each growth condition, and washed cells were normalized by cell number before addition to the PBMCs.
Bacteria (20 μl in phosphate buffered saline (PBS)) were added to each well of PBMCs to give the total number of bacteria as indicated for each experiment. Three different amounts of bacteria were tested: 1.25E+07, 6.25E+06, and 3.13E+06 were added to separate wells of PBMCs. A no-bacteria control also was run. All assays were done in triplicate. After a 2-day incubation at 37° C., the plates were spun at 300×g, and the supernatants were removed and stored frozen at −80° C. until analysis.
Cytokines in the culture supernatants were assayed using a 96-well assay kit from Meso Scale Discovery (Gaithersburg, Md.; catalog K15008B-1). Human Interleukin-1 beta (Il-1b), Interleukin 10 (I1-10), Interleukin 12p70 (Il112p70), and Tumor Necrosis Factor alpha (TNFa) 25 were quantitated and reported as picograms per milliliter. Each sample was assayed in duplicate.
FIGS. 2 to 5 show the results of a representative experiment. For each cytokine shown, B. infantis 35624 and BL1207 induce nearly identical levels of cytokines. These levels are very different than the levels induced by the three other Bifidobacterial strains that they were compared to.
Example 9
Bifidobacteria with Similar EPS Genes and High EPS Production Induce a Significantly Elevated IL-10:IL-12 Ratio Compared to Strains Lacking These Genes
Peripheral blood mononuclear cells (PBMCs) were isolated from healthy human peripheral blood using BD Vacutainer CPT tubes (BD catalog 362761), as per the manufacturer's instructions. PBMCs were washed and resuspended in Dulbecco's Modified Eagle Medium-GlutamaxTM (Glutamax (Glutamine substitute)+pyruvate+4.5 g/l glucose (Gibco catalog 10569-010) 10% fetal bovine serum (Sigma catalog F4135), and 1% penicillin/streptomycin (Sigma catalog P0781). PBMCs were incubated (2×105 cells per well) in flat-bottomed 96-well plates and 20 μL of a bacterial suspension (at a concentration of 1×107 CFU/mL) was added. PBMCs were co-incubated with bacteria for 48 hours at 37° C./5% CO2 in an incubator. After the 2 day incubation period, the plates were centrifuged at 300×g, and the supernatants were removed and stored frozen at −80° C. until analysis. Interleukin-10 (IL-10) and Interleukin-12p70 (IL-12p70) levels in the culture supernatants were quantified using a 96-well assay kit from Meso Scale Discovery (Gaithersburg, Md.; catalog K15008B-1)
Bacteria were prepared for co-culture experiments in two formats. (a) Freshly grown bacteria were grown in Difco MRS media and harvested just after entering into stationary phase. All cells were grown under anaerobic conditions at 37° C. (b) Bacteria were grown under anaerobic conditions at 37° C. in Difco MRS media and harvested just after entering into stationary phase. Freeze dried powders were generated for each of these bacteria and stored at −80° C. in pre-aliquoted 100 mg vials Immediately prior to their use, one aliquot of each strain was removed from the freezer and allowed to reach room temperature. Each strain was washed 3 times in 10 ml ringers followed by centrifugation. A fresh vial was used on each occasion. Growth curves (OD vs number of live cells) were constructed for each growth condition, and washed cells were normalized by cell number before addition to the PBMCs. A no-bacteria control was also included in all experiments. All assays were done in triplicate.
The Bifidobacteria which contained many of the EPS genes exhibited a similar effect on IL-10:IL-12 induction while bacterial strains which do not contain the EPS genes induced a significantly lower IL-10:IL-12 ratio (FIG. 13). Both freshly grown and freeze-dried cultures exhibited a similar effect in that the strains containing similar EPS genes induced a higher IL-10:IL-12 ratio than those strains that did not contain these genes.
The control of inflammatory diseases is exerted at a number of levels. The controlling factors include hormones, prostaglandins, reactive oxygen and nitrogen intermediates, leukotrienes and cytokines. Cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses. A number of cell types produce these cytokines, with neutrophils, monocytes and lymphocytes being the major sources during inflammatory reactions due to their large numbers at the injured site.
Multiple mechanisms exist by which cytokines generated at inflammatory sites influence the inflammatory response. Chemotaxis stimulates homing of inflammatory cells to the injured site, whilst certain cytokines promote infiltration of cells into tissue. Cytokines released within the injured tissue result in activation of the inflammatory infiltrate. Most cytokines are pleiotropic and express multiple biologically overlapping activities. As uncontrolled inflammatory responses can result in diseases such as IBD, it is reasonable to expect that cytokine production has gone astray in individuals affected with these diseases.
Interleukin-10 (IL-10) is an anti-inflammatory cytokine which is produced by many cell types including monocytes, macrophages, dendritic cells, mast cells and lymphocytes (in particular T regulatory cells). IL-10 down-regulates the expression of pro-inflammatory Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on antigen presenting cells. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway. Murine knock-out studies have demonstrated the essential role for IL-10 in immunoregulation as IL-10KO mice develop severe colitis. In addition, bacteria which are potent inducers of IL-10 have been shown to promote T regulatory cell differentiation in vivo thus contributing to immunological homeostasis (O'Mahony et al., AJP 2006; O'Mahony et al., PLoS Pathogens 2008).
Interleukin-12 (IL-12) is a pro-inflammatory cytokine associated with polarisation of Th1 effector T cell responses and stimulates the production of other pro-inflammatory Th1 cytokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), from T and natural killer (NK) cells. High levels of IL-12 expression is associated with autoimmunity. Administration of IL-12 to people suffering from autoimmune diseases was shown to worsen disease symptoms. In contrast, IL-12 knock-out mice or treatment of mice with IL-12 neutralising antibodies ameliorated the disease.
Cytokine cascades and networks control the inflammatory response, rather than the action of a particular cytokine on a particular cell type. The relative levels of expression, or balance, of two cytokines (such as IL-10 and IL-12) is more informative than the expression of a single cytokine. In these studies, we stimulated human PBMCs with a range of different bacterial strains. All strains induced IL-10 and all strains induced IL-12. However, examination of the ratio between IL-10 and IL-12 induction revealed that some bacterial strains induced a higher ratio (i.e. more IL-10 with less IL-12) compared to other strains. This is a meaningful observation as it is the balance between each of these opposing signals that ultimately determines the immunological outcome. It is anticipated that a high IL-10:IL-12 ratio would promote an anti-inflammatory response associated with appropriate immunoregulatory activity while a low IL-10:IL-12 ratio would contribute to Th1 polarisation of the immune response. Thus, the PBMC IL-10:IL-12 ratio is a important selection criterion for identification of bacterial strains with immunoregulatory properties.
The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as “40 mm” is intended to mean “about 40 mm.”
All documents cited in the Detailed Description of the Invention are, in relevant part, incorporated herein by reference; the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention. To the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.
While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.
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## Claims

1. A pharmaceutical ingestable carrier comprising more than 106 cfu per gram of the ingestable carrier of an isolated strain of Bifidobacterium longum BL1207 deposited at ATCC with accession number PTA-9608, wherein the pharmaceutical ingestable carrier is a tablet, and wherein the strain induces a ratio of interleukin-10 to interleukin-12 of at least 10 in a peripheral blood mononuclear cell co-incubation assay.

2. A pharmaceutical ingestable carrier comprising more than 106 cfu per gram of the ingestable carrier of an isolated strain of Bifidobacterium longum AH121A deposited at NCIMB with accession number NCIMB 41675, wherein the pharmaceutical ingestable carrier is a tablet, and wherein the strain induces a ratio of interleukin-10 to interleukin-12 of at least 10 in a peripheral blood mononuclear cell co-incubation assay.

3. A pharmaceutical ingestable carrier comprising more than 106 cfu per gram of the ingestable carrier of an isolated strain of Bifidobacterium longum AH1714 deposited at NCIMB with accession number NCIMB 41676, wherein the pharmaceutical ingestable carrier is a tablet, and wherein the strain induces a ratio of interleukin-10 to interleukin-12 of at least 10 in a peripheral blood mononuclear cell co-incubation assay.

4. A method of improving gastrointestinal health in a subject, the method comprising administering a composition comprising a therapeutically effective amount of the pharmaceutical ingestable carrier of claim 1.

5. A method of improving gastrointestinal health in a subject, the method comprising administering a composition comprising a therapeutically effective amount of the pharmaceutical ingestable carrier of claim 2.

6. A method of improving gastrointestinal health in a subject, the method comprising administering a composition comprising a therapeutically effective amount of the pharmaceutical ingestable carrier of claim 3.

7. A method for providing a probiotic to a subject, the method comprising administering a composition comprising a therapeutically effective amount of the pharmaceutical ingestable carrier of claim 1.

8. A method for providing a probiotic to a subject, the method comprising administering a composition comprising a therapeutically effective amount of the pharmaceutical ingestable carrier of claim 2.

9. A method for providing a probiotic to a subject, the method comprising administering a composition comprising a therapeutically effective amount of the pharmaceutical ingestable carrier of claim 3.