bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics of Central Carbon Metabolism in
Mycobacterium tuberculosis
Authors: Baughn Anthony D. , Rhee Kyu Y. 
Published: October 2014

ABSTRACT

Metabolism is a biochemical activity of all cells, thought to fuel the physiologic needs of a given cell in a quantitative, rather than qualitatively specific, manner.
Mycobacterium tuberculosis
is a chronic facultative intracellular pathogen that resides in humans as its only known host and reservoir. Within humans,
M. tuberculosis
resides chiefly in the macrophage phagosome, the cell type and compartment most committed to its eradication.
M. tuberculosis
thus occupies the majority of its decades-long life cycle in a state of slowed or arrested replication. At the same time,
M. tuberculosis
remains poised to reenter the cell cycle to ensure its propagation as a species.
M. tuberculosis
has thus evolved its metabolic network to both maintain and propagate its survival as a species within a single host. Knowledge of the specific ways in which its metabolic network serves these distinct though interdependent functions, however, remains highly incomplete. In this article we review existing knowledge of
M. tuberculosis
's central carbon metabolism as reported by studies of its basic genetic and biochemical composition, regulation, and organization, with the hope that such knowledge will inform our understanding of
M. tuberculosis
's ability to traverse the stringent and heterogeneous niches encountered in the host.
Genetic Strategies for Identifying New Drug Targets
Authors: Trauner Andrej , Sassetti Christopher M. , Rubin Eric J. 
Published: October 2014

ABSTRACT
Genetic strategies have yet to come into their own as tools for antibiotic development. While holding a lot of initial promise, they have only recently started to bear fruit in the quest for new drug targets. An ever-increasing body of knowledge is showing that genetics can lead to significant improvements in the success and efficiency of drug discovery. Techniques such as high-frequency transposon mutagenesis and expression modulation have matured and have been applied successfully not only to the identification and characterization of new targets, but also to their validation as tractable weaknesses of bacteria. Past experience shows that choosing targets must not rely on gene essentiality alone, but rather needs to incorporate knowledge of the system as a whole. The ability to manipulate genes and their expression is key to ensuring that we understand the entire set of processes that are affected by drug treatment. Focusing on exacerbating these perturbations, together with the identification of new targets to which resistance has not yet occurred—both enabled by genetic approaches—may point us toward the successful development of new combination therapies engineered based on underlying biology.
The Spectrum of Drug Susceptibility in Mycobacteria
Authors: Aldridge Bree B. , Keren Iris , Fortune Sarah M. 
Published: October 2014

ABSTRACT
A major factor complicating efforts to control the tuberculosis epidemic is the long duration of treatment required to successfully clear the infection. One reason that long courses of treatment are required may be the fact that mycobacterial cells arise during the course of infection that are less susceptible to antibiotics. Here we describe the paradigms of phenotypic drug tolerance and resistance as they apply to mycobacteria. We then discuss the mechanisms by which phenotypically drug-tolerant and -resistant cells arise both at a population level and in specialized subpopulations of cells that may be especially important in allowing the bacterium to survive in the face of treatment. These include general mechanisms that have been shown to alter the susceptibility of mycobacteria to antibiotics including growth arrest, efflux pump induction, and biofilm formation. In addition, we discuss emerging data from single-cell studies of mycobacteria that have identified unique ways in which specialized subpopulations of cells arise that vary in their frequency, in their susceptibility to drug, and in their stability over time.
The Partitioning and Copy Number Control Systems of the Selfish Yeast Plasmid: An Optimized Molecular Design for Stable Persistence in Host Cells
Authors: Liu Yen-Ting , Sau Saumitra , Ma Chien-Hui , Kachroo Aashiq H , Rowley Paul A , Chang Keng-Ming , Fan Hsiu-Fang , Jayaram Makkuni 
Published: October 2014

ABSTRACT

The multicopy 2-micron plasmid of
Saccharomyces cerevisiae
, a resident of the nucleus, is remarkable for its high chromosome-like stability. The plasmid does not appear to contribute to the fitness of the host, nor does it impose a significant metabolic burden on the host at its steady state copy number. The plasmid may be viewed as a highly optimized selfish DNA element whose genome design is devoted entirely to efficient replication, equal segregation, and copy number maintenance. A partitioning system comprised of two plasmid-coded proteins, Rep1 and Rep2, and a partitioning locus,
STB
, is responsible for equal or nearly equal segregation of plasmid molecules to mother and daughter cells. Current evidence supports a model in which the Rep-
STB
system promotes the physical association of the plasmid with chromosomes and thus plasmid segregation by a hitchhiking mechanism. The Flp site-specific recombination system housed by the plasmid plays a critical role in maintaining a steady state plasmid copy number. A decrease in plasmid population due to rare missegregation events is rectified by plasmid amplification via a recombination-induced rolling circle-like replication mechanism. Appropriate plasmid amplification, without a runaway increase in copy number, is ensured by positive and negative regulation of
FLP
gene expression by plasmid-coded proteins and by the control of Flp level/activity through host-mediated posttranslational modification(s) of Flp. The Flp system has been successfully utilized to understand mechanisms of site-specific recombination, to bring about directed genetic alterations for addressing fundamental problems in biology, and as a tool in biotechnological applications.
Conjugation in Gram-Positive Bacteria
Authors: Goessweiner-Mohr Nikolaus , Arends Karsten , Keller Walter , Grohmann Elisabeth 
Published: October 2014

ABSTRACT

Conjugative transfer is the most important means of spreading antibiotic resistance and virulence factors among bacteria. The key vehicles of this horizontal gene transfer are a group of mobile genetic elements, termed conjugative plasmids. Conjugative plasmids contain as minimum instrumentation an origin of transfer (
oriT
), DNA-processing factors (a relaxase and accessory proteins), as well as proteins that constitute the
trans
-envelope transport channel, the so-called mating pair formation (Mpf) proteins. All these protein factors are encoded by one or more transfer
(tra
) operons that together form the DNA transport machinery, the Gram-positive type IV secretion system. However, multicellular Gram-positive bacteria belonging to the streptomycetes appear to have evolved another mechanism for conjugative plasmid spread reminiscent of the machinery involved in bacterial cell division and sporulation, which transports double-stranded DNA from donor to recipient cells. Here, we focus on the protein key players involved in the plasmid spread through the two different modes and present a new secondary structure homology-based classification system for type IV secretion protein families. Moreover, we discuss the relevance of conjugative plasmid transfer in the environment and summarize novel techniques to visualize and quantify conjugative transfer in situ.
The Interplay between Different Stability Systems Contributes to Faithful Segregation:Streptococcus pyogenespSM19035 as a Model
Authors: Volante Andrea , Soberón Nora E. , Ayora Silvia , Alonso Juan C. 
Published: October 2014

ABSTRACTTheStreptococcus pyogenespSM19035 low-copy-number θ-replicating plasmid encodes five segregation (seg) loci that contribute to plasmid maintenance. These loci map outside of the minimal replicon. ThesegAlocus comprises β2recombinase and twosixsites, andsegCincludessegAand also the γ topoisomerase and twossiAsites. Recombinase β2plays a role both in maximizing random segregation by resolving plasmid dimers (segA) and in catalyzing inversion between two inversely orientedsixsites.segA, in concert withsegC, facilitates replication fork pausing atssiAsites and overcomes the accumulation of “toxic” replication intermediates. ThesegB1locus encodes ω, ε, and ζ genes. The short-lived ε2antitoxin and the long-lived ζ toxin form an inactive ζε2ζ complex. Free ζ toxin halts cell proliferation upon decay of the ε2antitoxin and enhances survival. If ε2expression is not recovered, by loss of the plasmid, the toxin raises lethality. ThesegB2locus comprises δ and ω genes and sixparSsites. Proteins δ2and ω2, by forming complexes withparSand chromosomal DNA, pair the plasmid copies at the nucleoid, leading to the formation of a dynamic δ2gradient that separates the plasmids to ensure roughly equal distribution to daughter cells at cell division. ThesegDlocus, which comprises ω2(or ω2plus ω22) andparSsites, coordinates expression of genes that control copy number, better-than-random segregation, faithful partition, and antibiotic resistance. The interplay of thesegloci and with thereplocus facilitates almost absolute plasmid stability.
The Influence of Biofilms in the Biology of Plasmids
Authors: Cook Laura C.C. , Dunny Gary M. 
Published: October 2014

ABSTRACT
The field of plasmid biology has historically focused on bacteria growing in liquid culture. Surface-attached communities of bacterial biofilms have recently been understood to be the normal environment of bacteria in the natural world. Thus, studies examining plasmid replication, maintenance, and transfer in biofilms are essential for a true understanding of bacterial plasmid biology. This article reviews the current knowledge of the interplay between bacterial biofilms and plasmids, focusing on the role of plasmids in biofilm development and the role of biofilms in plasmid maintenance, copy-number control, and transfer. The studies examined herein highlight the importance of biofilms as an important ecological niche in which bacterial plasmids play an essential role.
Sporulation in Bacteria: Beyond the Standard Model
Authors: Hutchison Elizabeth A. , Miller David A. , Angert Esther R. 
Published: October 2014

ABSTRACT

Endospore formation follows a complex, highly regulated developmental pathway that occurs in a broad range of
Firmicutes
. Although
Bacillus subtilis
has served as a powerful model system to study the morphological, biochemical, and genetic determinants of sporulation, fundamental aspects of the program remain mysterious for other genera. For example, it is entirely unknown how most lineages within the
Firmicutes
regulate entry into sporulation. Additionally, little is known about how the sporulation pathway has evolved novel spore forms and reproductive schemes. Here, we describe endospore and internal offspring development in diverse
Firmicutes
and outline progress in characterizing these programs. Moreover, comparative genomics studies are identifying highly conserved sporulation genes, and predictions of sporulation potential in new isolates and uncultured bacteria can be made from these data. One surprising outcome of these comparative studies is that core regulatory and some structural aspects of the program appear to be universally conserved. This suggests that a robust and sophisticated developmental framework was already in place in the last common ancestor of all extant
Firmicutes
that produce internal offspring or endospores. The study of sporulation in model systems beyond
B. subtilis
will continue to provide key information on the flexibility of the program and provide insights into how changes in this developmental course may confer advantages to cells in diverse environments.
Burn injury, gender and cancer risk: population-based cohort study using data from Scotland and Western Australia
Authors: Duke Janine M , Bauer Jacqui , Fear Mark W , Rea Suzanne , Wood Fiona M , Boyd James 
Published: October 2014

ObjectiveTo investigate the risk of cancer and potential gender effects in persons hospitalised with burn injury.DesignPopulation-based retrospective cohort study using record-linkage systems in Scotland and Western Australia.ParticipantsRecords of 37 890 and 23 450 persons admitted with a burn injury in Scotland and Western Australia, respectively, from 1983 to 2008. Deidentified extraction of all linked hospital morbidity records, mortality and cancer records were provided by the Information Service Division Scotland and the Western Australian Data Linkage Service.Main outcome measuresTotal and gender-specific number of observed and expected cases of total (‘all sites’) and site-specific cancers and standardised incidence ratios (SIRs).ResultsFrom 1983 to 2008, for female burn survivors, there was a greater number of observed versus expected notifications of total cancer with 1011 (SIR, 95% CI 1.3, 1.2 to 1.4) and 244 (SIR, 95% CI 1.12, 1.05 to 1.30), respectively, for Scotland and Western Australia. No statistically significant difference in total cancer risk was found for males. Significant excesses in observed cancers among burn survivors (combined gender) in Scotland and Western Australian were found for buccal cavity, liver, larynx and respiratory tract and for cancers of the female genital tract.ConclusionsResults from the Scotland data confirmed the increased risk of total (‘all sites’) cancer previously observed among female burn survivors in Western Australia. The gender dimorphism observed in this study may be related to the role of gender in the immune response to burn injury. More research is required to understand the underlying mechanism(s) that may link burn injury with an increased risk of some cancers.
Efficacy of a recombinant equine influenza vaccine against challenge with an American lineage H3N8 influenza virus responsible for the 2003 outbreak in the United Kingdom
Authors: Edlund Toulemonde C. , Daly J. , Sindle T. , Guigal P. M. , Audonnet J. C. , Minke J. M. 
Published: October 2014

Fifteen influenza‐naive Welsh mountain ponies were randomly assigned to three groups of five. A single dose of a recombinant ALVAC vaccine was administered intramuscularly to five of the ponies, two doses, administered five weeks apart, were administered to five, and the other five served as unvaccinated, challenge controls. Two weeks after the completion of the vaccination programme, the ponies were all challenged by exposure to an aerosol of influenza virus A/eq/Newmarket/5/03. Their clinical signs were scored daily for 14 days according to a standardised scoring protocol, and nasal swabs were taken daily for 10 days to monitor the excretion of virus. The challenge produced severe clinical signs of influenza (fever, coughing, nasal discharge and dyspnoea) in all five control ponies, but the vaccinated ponies developed only mild disease, consisting of a serous nasal discharge lasting for only one day. The excretion of virus was almost completely suppressed in the vaccinated ponies, but the control ponies shed the virus for up to seven days after the challenge.
Laboratory model to evaluate the role of aerosols in the transport of porcine reproductive and respiratory syndrome virus
Authors: A. Dee S. , Deen J. , Jacobson L. , Rossow K. D. , Mahlum C. , Pijoan C. 
Published: October 2014

The aim of this study was to develop a model to evaluate the aerosol transmission of porcine reproductive and respiratory disease virus (PRRSV). PRRSV (MN 30‐100 strain, total dose 3 × 106 virus particles) was aerosolised and transported up to 150 m and a portable air sampler was used to collect air samples at 1, 30, 60, 90, 120 and 150 m (five replicates at each distance) and the air samples were tested by TaqMan PCR and virus isolation. The infectivity of the aerosolised PRRSV was tested by exposing six PRRSV ‐naive pigs for three hours to aerosolised virus that had been transported 150 m. PRRSV RNA was detected in all five replicate air samples collected at 1, 30, 60 and 90 m, in four of the five collected at 120 m, and in three of the five collected at 150 m. Infectious PRRSV was detected by virus isolation at 1 and 30 m (all five replicates), 60, 90 and 120 m (three of the five) and 150 m (two of the five). There was a 50 per cent reduction in the log concentration of PRRSV RNA every 33 m. Three of the six pigs exposed to PRRSV ‐positive aerosols became infected, and PRRSV RNA was detected in air samples and on swab samples collected from the interior of the chambers that housed the infected pigs while they were being exposed.
Suspected adverse reactions, 2004
Authors: Dyer F. , Mulugeta R. , Spagnuolo‐Weaver M. , Tait A. 
Published: October 2014

Reports to the UK Suspected Adverse Reaction Surveillance Scheme (SARSS) in 2004 increased by 22 per cent compared with 2003
The number of reports involving dogs, cats and cattle increased, while there were fewer reports involving sheep and rabbits
A suspected lack of efficacy in cattle was largely responsible for the significant increase in the overall total number of reports for this species
Fewer human suspected adverse reactions were reported in 2004 than 2003
– These are some of the findings under the SARSS in 2004, as discussed in the following article by Fabia Dyer, Rahel Mulugeta, Martha Spagnuolo‐Weaver and Alex Tait of the Veterinary Medicines Directorate
Hypocalcaemia due to nutritional calcium deficiency and hypoparathyroidism in an adult dog
Authors: Diquélou A. , Chaput C. , Priymenko N. , Benoit E. 
Published: October 2014

A 13‐year‐old intact male poodle had suffered periodic tetanic crises for two months. It was cachectic and moderately dehydrated, and during the crises blindness, a stiff gait and behavioural changes were observed. Routine haematological and biochemical profiles showed that it was severely hypocalcaemic, with a corrected plasma calcium concentration of 1·13 mmol/litre (reference range 2·25 to 3 mmol/litre). The dog was fed a home‐made diet composed of chicken and basmati rice cooked with a soup bouillon cube; an analysis of its daily allowance indicated that the dog was generally malnourished and received only 0·222 g of calcium per day rather than the 0·6 g it required. In addition, the dog had a low blood concentration of parathyroid hormone of 12 ng/litre (reference range 20 to 80 ng/litre). Supplementing the dog with calcitriol for four days and correcting its diet increased its blood calcium to the lower part of the reference range and resolved the clinical signs, although its parathyroid hormone concentration was still low one year later.
The 2001 epidemic of foot‐and‐mouth disease in the United Kingdom: epidemiological and meteorological case studies
Authors: Gloster J. , Champion H. J. , Mansley L. M. , Romero P. , Brough T. , Ramirez A. 
Published: October 2014

The possibility of the airborne spread of foot‐and‐mouth disease during the 2001 epidemic in the UK has been investigated in three epidemiological case studies. On the basis of evidence from field investigations, and a simple meteorological analysis, it is concluded that the spread of disease was consistent with the airborne transport of virus. The distances ranged from less than 1 km to 16 km; six of the farms were over 6 km from the source and involved the passage of virus over the sea combined with meteorological conditions which strongly favoured airborne disease transmission. The results of detailed atmospheric modelling demonstrated that airborne virus could have challenged livestock on all the farms studied. However, with one exception the 24‐hour average daily concentrations of the virus were significantly below the experimentally estimated threshold for infection. A detailed model intercomparison established that, under stable atmospheric conditions, peak concentrations of virus up to two orders of magnitude higher might have been experienced for short periods, owing to fluctuations within the plume of virus, and model limitations. This finding would significantly reduce the apparent discrepancy between the experimentally estimated threshold for infection and the modelling results.
Prevalence and associations between bacterial isolates from dry mammary glands of dairy cows
Authors: Green M. J. , Green L. E. , Medley G. F. , Bradley A. J. , Burton P. R. , Schukken Y. H. 
Published: October 2014

To assess the prevalence and patterns of bacterial isolates, cultures were made from the dry mammary glands of dairy cows in six commercial dairy herds in the UK. Milk samples were taken from all four quarters of 480 cows at drying off and at weekly intervals from 14 days before to seven days after calving. A major mastitis pathogen was isolated from at least one quarter of 220 (45·8 per cent) of the cows and from more than one quarter of 90 (18·8 per cent) of them. During the late dry to calving period, of the 957 quarters with three culture results, a major mastitis pathogen was cultured from 236 (24·7 per cent) quarters of 186 (88·8 per cent) cows. The most commonly isolated major pathogen wasEscherichia coli, followed byStreptococcus uberisand coagulase‐positive staphylococci. There were significant differences between the patterns of isolates from different farms and in different calving months, suggesting that the rate of infection was partially dependent on external conditions. The isolation ofE coli, S uberisor coagulasepositive staphylococci from a cow during the late dry/periparturient period was associated with an increased risk of that cow being culled in the next lactation. Bayesian general linear mixed models were used to assess the associations between the different bacterial species. The probability of isolating eitherE coli or S uberiswas significantly greater when the other organism was cultured in a milk sample; this was also true of coagulase‐positive staphylococci andS uberis. WhenCorynebacteriumspecies were isolated from a milk sample, the probability of isolating coagulase‐positive staphylococci orS uberisdecreased significantly, and when coagulase‐negative staphylococci were isolated the probability of isolating coagulase‐positive staphylococci was reduced.
Isolation of bovine adenovirus serotype 6 from a calf in the United Kingdom
Authors: Graham D. A. , Calvert V. , Curran W. , Wylie M. , Snodden D.A. , Moffet D. A. , Adair B. M. , Smyth J. A. , Benkö M. , Papp T. 
Published: October 2014

Two viruses, designated 99–8130(C) and 99–8130(I), were isolated in calf testis cells from the colon and ileum, respectively, of a suckled beef calf which had developed dysentery and died. Electron microscopy indicated that the mean (sd) size of the viral particles, 83 (2·5) nm, and their morphology were consistent with their being members of the family Adenoviridae. They were confirmed as adenoviruses by PCR when products of the expected size (608 bp) were amplified from both isolates by using a primer pair specific for members of the genusAtadenovirus. A comparison of the sequence of a 567 bp segment of the 99–8130(C) amplicon with that of other prototype bovine adenovirus (BAdV) strains of atadenoviruses identified the isolate as BAdV serotype 6 (BAdV–6), which had 99·3 per cent and 100 per cent identities at the nucleotide and amino acid levels, respectively, with the prototype BAdV–6 strain 671130. A virus neutralisation test was developed and indicated a high prevalence of antibody to BAdV–6 in Northern Irish cattle. There was no evidence of adenoviral inclusions in tissues from the affected calf and no antigen was detected when the tissues were stained by an immunoperoxidase technique, using a homologous antiserum raised in rabbits. The two viruses were the third reported isolation of BAdV–6, and the first from a clinically ill bovine animal.