bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a Whole Genome Approach To Identify Vaccine Molecules Affording Protection against
Streptococcus pneumoniae
Infection
Authors: Wizemann Theresa M. , Heinrichs Jon H. , Adamou John E. , Erwin Alice L. , Kunsch Charles , Choi Gil H. , Barash Steven C. , Rosen Craig A. , Masure H. Robert , Tuomanen Elaine , Gayle Anthony , Brewah Yambasu A. , Walsh William , Barren Philip , Lathigra Raju , Hanson Mark , Langermann Solomon , Johnson Syd , Koenig Scott 
Published: July 2002

ABSTRACT

Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding. Exploiting the whole genome sequence of the human bacterial pathogen
Streptococcus pneumoniae
, we identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors. Mice were immunized with 108 of these proteins, and 6 conferred protection against disseminated
S. pneumoniae
infection. Flow cytometry confirmed the surface localization of several of these targets. Each of the six protective antigens showed broad strain distribution and immunogenicity during human infection. Our results validate the use of a genomic approach for the identification of novel microbial targets that elicit a protective immune response. These new antigens may play a role in the development of improved vaccines against
S. pneumoniae
.
Passive Antibody toBartonella henselaeProtects against Clinical Disease following Homologous Challenge but Does Not Prevent Bacteremia in Cats
Authors: O'Reilly Kathy L. , Parr Katy A. , Brown Tracy P. , Tedder-Ferguson Belinda , Scholl Daniel T. 
Published: July 2002

ABSTRACTWe challenged cats transfused with anti-Bartonellaserum and kittens born to antibody-positive queens withBartonella henselaeto determine the contribution of antibodies to the control ofB. henselaein cats. In both experiments, antibody-positive cats were protected from clinical disease but passive antibody to the homologous strain ofB. henselaedid not prevent bacteremia.
Monocytes Augment Bacterial Species- and Strain-Dependent Induction of Tissue Factor Activity in Bacterium-Infected Human Vascular Endothelial Cells
Authors: Veltrop M. H. A. M. , Thompson J. , Beekhuizen H. 
Published: July 2002

ABSTRACTIn bacterial endocarditis (BE), intravascular infection withStaphylococcus aureus,Streptococcus sanguis,orStaphylococcus epidermidiscan lead to formation of a fibrin clot on the inner surface of the heart and cause heart dysfunction. The events that start the coagulation in the early stage of the disease are largely unknown. We have recently shown that human endothelial cells (EC) upon binding and internalization ofS. aureus, but notS. sanguisorS. epidermidis, express tissue factor (TF)-dependent procoagulant activity (TFA). The present study shows that infection of EC with these three pathogens induces surface expression of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and monocyte adhesion. Subsequent coculture of these cells synergistically enhanced TFA, which was exclusively dependent on TF molecules that were expressed on EC during coculture. TFA induction required direct contact between monocytes and bacterium-infected EC, but the signals for this response were not generated by the binding of monocytes through their β2- or α4-integrins to ICAM-1 or VCAM-1, respectively, on infected EC. The mechanism by which monocytes induce TFA in bacterium-infected EC was partly mediated by the proinflammatory cytokine interleukin-1 produced by the cells during coculture. Endogenous tumor necrosis factor alpha was not involved. This modulating effect of monocytes on species- and strain-dependent TFA of bacterium-infected EC supports our hypothesis that in an early stage in the pathogenesis of BE, as well as other intravascular infections that lead to detrimental fibrin formation, the coagulation cascade can be activated on the surfaces of EC as a consequence of specific interactions between pathogenic bacteria, EC, and monocytes.
Pneumolysin Potentiates Production of Prostaglandin E
2
and Leukotriene B
4
by Human Neutrophils
Authors: Cockeran Riana , Steel Helen C. , Mitchell Timothy J. , Feldman Charles , Anderson Ronald 
Published: July 2002

ABSTRACT

Exposure to pneumolysin (8.37 and 41.75 ng/ml) caused a calcium-dependent increase in the generation of prostaglandin E
2
and leukotriene B
4
by both resting and chemoattractant-activated human neutrophils in vitro. These interactions of pneumolysin with neutrophils may result in dysregulation of inflammatory responses during pneumococcal infection.
Evolutionary Relationships among Virulence-Associated Histidine Kinases
Authors: Brinkman Fiona S. L. , Macfarlane Emma L. A. , Warrener Paul , Hancock Robert E. W. 
Published: July 2002

ABSTRACT

A strong relationship between virulence-associated sensor histidine kinases of fungi and those in
Streptomyces coelicolor
was observed, and phylogenetic analysis suggested that bacterium-to-eukaryote horizontal gene transfer had occurred between ancestors of these organisms. Phylogenetic analysis also identified a group of histidine kinases orthologous to the
Streptomyces
proteins that includes
Pseudomonas aeruginosa
GacS. We provide evidence that GacS is important for swarming motility, lipase production, and virulence in mice and had evolved to have partial functional overlaps with PhoQ, a less-related virulence-associated histidine kinase.
Kinetics ofBartonella birtlesiiInfection in Experimentally Infected Mice and Pathogenic Effect on Reproductive Functions
Authors: Boulouis Henri J. , Barrat Francine , Bermond Delphine , Bernex Florence , Thibault Danièle , Heller Rémy , Fontaine Jean-Jacques , Piémont Yves , Chomel Bruno B. 
Published: July 2002

ABSTRACTThe kinetics of infection and the pathogenic effects on the reproductive function of laboratory mice infected withBartonella birtlesiirecovered from anApodemusspecies are described.B. birtlesiiinfection, as determined by bacteremia, occurred in BALB/c mice inoculated intravenously. Inoculation with a low-dose inoculum (1.5 × 103CFU) induced bacteremia in only 75% of the mice compared to all of the mice inoculated with higher doses (≥1.5 × 104). Mice became bacteremic for at least 5 weeks (range, 5 to 8 weeks) with a peak ranging from 2 × 103to 105CFU/ml of blood. The bacteremia level was significantly higher in virgin females than in males but the duration of bacteremia was similar. In mice infected before pregnancy (n= 20), fetal loss was evaluated by enumerating resorption and fetal death on day 18 of gestation. The fetal death and resorption percentage of infected mice was 36.3% versus 14.5% for controls (P< 0.0001). Fetal suffering was evaluated by weighing viable fetuses. The weight of viable fetuses was significantly lower for infected mice than for uninfected mice (P< 0.0002). Transplacental transmission ofBartonellawas demonstrated since 76% of the fetal resorptions tested was culture positive forB. birtlesii. The histopathological analysis of the placentas of infected mice showed vascular lesions in the maternal placenta, which could explain the reproductive disorders observed. BALB/c mice appeared to be a useful model for studyingBartonellainfection. This study provides the first evidence of reproductive disorders in mice experimentally infected with aBartonellastrain originating from a wild rodent.
Specific Expression ofAnaplasma marginaleMajor Surface Protein 2 Salivary Gland Variants Occurs in the Midgut and Is an Early Event during Tick Transmission
Authors: Löhr Christiane V. , Rurangirwa Fred R. , McElwain Terry F. , Stiller David , Palmer Guy H. 
Published: July 2002

ABSTRACTInfectivity ofAnaplasmaspp. develops when infected ticks feed on a mammalian host (transmission feed). SpecificAnaplasma marginalemajor surface protein 2 (MSP2) variants are selected for within the tick and are expressed within the salivary glands. The aims of this study were to determine when and where MSP2 variant selection occurs in the tick, how MSP2 expression is regulated in salivary glands of transmission-feeding ticks, and whether the number ofA. marginaleorganisms per salivary gland is significantly increased during transmission feeding. The South Idaho strain ofA. marginalewas used, as MSP2 expression is restricted to two variants, SGV1 and SGV2, inDermacentor andersoni.Using Western blot, real-time PCR, and DNA sequencing analyses it was shown that restriction and expression of MSP2 occurs early in the midgut within the first 48 h of the blood meal, when ticks acquire infection.A. marginaleis present in the tick salivary glands before transmission feeding is initiated, but themsp2mRNA and MSP2 protein levels perA. marginaleorganism increase only minimally and transiently in salivary glands of transmission-feeding ticks compared to that of unfed ticks.A. marginalenumbers per tick increase gradually in salivary glands of both transmission-fed and unfed ticks. It is concluded that MSP2 variant selection is an early event in the tick and that MSP2 variants SGV1 and SGV2 are expressed both in the midgut and salivary glands. While MSP2 may be required for infectivity, there is no strict temporal correlation between MSP2 expression and the development of infectivity.
Mapping Antigenic Sites of an Immunodominant Surface Lipoprotein of
Mycoplasma agalactiae
, AvgC, with the Use of Synthetic Peptides
Authors: Santona Antonella , Carta Franco , Fraghí Peppinetta , Turrini Franco 
Published: July 2002

ABSTRACT

As a first step toward the design of an epitope vaccine to prevent contagious agalactia, the strongly immunogenic 55-kDa protein of
Mycoplasma agalactiae
was studied and found to correspond to the AvgC protein encoded by the
avgC
gene. The
avg
genes of
M. agalactiae
, which encode four variable surface lipoproteins, display a significant homology to the
vsp
(variable membrane surface lipoproteins) genes of the bovine pathogen
Mycoplasma bovis
at their promoter region as well as their N-terminus-encoding regions. Some members of the Vsp family are known to be involved in cytoadhesion to host cells. In order to localize immunogenic peptides in the AvgC antigen, the protein sequence was submitted to epitope prediction analysis, and five sets of overlapping peptides, corresponding to five selected regions, were synthesized by Spot synthesis. Reactive peptides were selected by immunobinding assay with sera from infected sheep. The three most immunogenic epitopes were shown to be surface exposed by immunoprecipitation assays, and one of these was specifically recognized by all tested sera. Our study indicates that selected epitopes of the AvgC lipoprotein may be used to develop a peptide-based vaccine which is effective against
M. agalactiae
infection.
Antigenic Variation ofEhrlichia chaffeensisResulting from Differential Expression of the 28-Kilodalton Protein Gene Family
Authors: Long S. Wesley , Zhang Xiao-Feng , Qi Hai , Standaert Steven , Walker David H. , Yu Xue-Jie 
Published: July 2002

ABSTRACTThe transcriptional activity and allele variation of the 28-kDa outer membrane protein gene (p28) ofEhrlichia chaffeensiswere analyzed to determine the mechanism of the antigenic variation of the 28-kDa outer membrane proteins. Reverse transcriptase PCR amplification of mRNA indicated that 16 of the 22 members of thep28multigene family were transcribed. Amino acid sequence analysis indicated that the p28-19 protein was produced in vitro in the Arkansas strain. Thep28-19gene and its promoter region were sequenced and compared in 12 clinical isolates ofE. chaffeensisto determine allele variation. The variation of thep28-19gene among the isolates is limited to three types represented by strains Arkansas, 91HE17, and Sapulpa, respectively. These results indicate that the majority of thep28genes are active genes and that antigenic variation of theE. chaffeensis28-kDa proteins may result from differential expression of thep28gene family members rather than gene conversion.
NikR Mediates Nickel-Responsive Transcriptional Induction of Urease Expression inHelicobacter pylori
Authors: van Vliet Arnoud H. M. , Poppelaars Sophie W. , Davies Beverly J. , Stoof Jeroen , Bereswill Stefan , Kist Manfred , Penn Charles W. , Kuipers Ernst J. , Kusters Johannes G. 
Published: July 2002

ABSTRACTThe important human pathogenHelicobacter pylorirequires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity ofH. pyloriurease were previously demonstrated to be induced by nickel supplementation of growth media. Here it is demonstrated that the HP1338 protein, an ortholog of theEscherichia colinickel regulatory protein NikR, mediates nickel-responsive induction of urease expression inH. pylori. Mutation of the HP1338 gene (nikR) ofH. pyloristrain 26695 resulted in significant growth inhibition of thenikRmutant in the presence of supplementation with NiCl2at ≥100 μM, whereas the wild-type strain tolerated more than 10-fold-higher levels of NiCl2. Mutation ofnikRdid not affect urease subunit expression or urease enzyme activity in unsupplemented growth media. However, the nickel-induced increase in urease subunit expression and urease enzyme activity observed in wild-typeH. pyloriwas absent in theH. pylori nikRmutant. A similar lack of nickel responsiveness was observed upon removal of a 19-bp palindromic sequence in theureApromoter, as demonstrated by using a genomicureA::lacZreporter gene fusion. In conclusion, theH. pyloriNikR protein and a 19-bp operator sequence in theureApromoter are both essential for nickel-responsive induction of urease expression inH. pylori.
Protective Immunity Conferred by AttenuatedaroADerivatives ofPasteurella multocidaB:2 Strains in a Mouse Model of Hemorrhagic Septicemia
Authors: Tabatabaei Mohammad , Liu Zhiqi , Finucane Anna , Parton Roger , Coote John 
Published: July 2002

ABSTRACTHemorrhagic septicemia (HS) is a fatal systemic disease of cattle and buffaloes. In South Asia HS is caused by infection withPasteurella multocidaserotype B:2. Some control is achieved with alum-precipitated or oil-adjuvanted killed whole-cell vaccines injected subcutaneously, but these vaccines provide only short-term immunity and require annual administration for effective use. Live attenuated vaccines have the advantage of a natural route of entry into the host, but for live strains to be used as vaccines, the mode of attenuation should be well defined. We constructedaroAattenuated derivatives of twoP. multocidaserotype B:2 strains by allelic exchange of the nativearoAsequence witharoAsequences disrupted with a kanamycin resistance cassette or with marker-freearoAsequences containing an internal deletion. These strains were confirmed to bearoAmutants by PCR and Southern blot analysis, enzyme assay, and lack of growth on minimal medium. ThearoAderivatives were highly attenuated for virulence in a mouse model of HS. Mouse challenge experiments showed that intraperitoneal or intranasal vaccination of anaroAstrain completely protected mice against challenge with a high dose (>1,000 50% lethal doses) of either the parent strain or the other wild-type B:2 strain. The spread of the parent and thearoAderivatives to different organs was compared when the organisms were inoculated by different routes.
A Dispensable Role for Forespore-Specific Gene Expression in Engulfment of the Forespore during Sporulation of
Bacillus subtilis
Authors: Sun Ya-Lin , Sharp Marc D. , Pogliano Kit 
Published: July 2002

ABSTRACT

During the stage of engulfment in the
Bacillus subtilis
spore formation pathway, the larger mother cell engulfs the smaller forespore. We have tested the role of forespore-specific gene expression in engulfment using two separate approaches. First, using an assay that unambiguously detects sporangia that have completed engulfment, we found that a mutant lacking the only forespore-expressed engulfment protein identified thus far, SpoIIQ, is able to efficiently complete engulfment under certain sporulation conditions. However, we have found that the mutant is defective, under all conditions, in the expression of the late-forespore-specific transcription factor ς
G
; thus, SpoIIQ is essential for spore production. Second, to determine if engulfment could proceed in the absence of forespore-specific gene expression, we made use of a strain in which activation of the mother cell-specific sigma factor ς
E
was uncoupled from forespore-specific gene expression. Remarkably, engulfment occurred in the complete absence of ς
F
-directed gene expression under the same conditions permissive for engulfment in the absence of SpoIIQ. Our results demonstrate that forespore-specific gene expression is not essential for engulfment, suggesting that the machinery used to move the membranes around the forespore is within the mother cell.
Analysis of the SOS Response in
Salmonella enterica
Serovar Typhimurium Using RNA Fingerprinting by Arbitrarily Primed PCR
Authors: Benson Nicholas R. , Wong Rita M.-Y. , McClelland Michael 
Published: July 2002

ABSTRACT

We report an analysis of a sample of the SOS response of
Salmonella enterica
serovar Typhimurium using the differential display of RNA fingerprinting gels of arbitrarily primed PCR products. The SOS response was induced by the addition of mitomycin C to an exponentially growing culture of serovar Typhimurium, and the RNA population was sampled during the following 2 h. These experiments revealed 21 differentially expressed PCR fragments representing mRNA transcripts. These 21 fragments correspond to 20 distinct genes. All of these transcripts were positively regulated, with the observed induction starting 10 to 120 min after addition of mitomycin C. Fifteen of the 21 transcripts have no homologue in the public sequence data banks and are therefore classified as novel. The remaining six transcripts corresponded to the
recE
,
stpA
,
sulA
, and
umuC
genes, and to a gene encoding a hypothetical protein in the
Escherichia coli lysU-cadA
intergenic region; the
recE
gene was represented twice by nonoverlapping fragments. In order to determine if the induction of these 20 transcripts constitutes part of a classical SOS regulon, we assessed the induction of these genes in a
recA
mutant. With one exception, the increased expression of these genes in response to mitomycin C was dependent on the presence of a functional
recA
allele. The exception was fivefold induced in the absence of a functional RecA protein, suggesting another layer of regulation in response to mitomycin C, in addition to the RecA-LexA pathway of SOS induction. Our data reveal several genes belonging to operons known to be directly involved in pathogenesis. In addition, we have found several phage-like sequences, some of which may be landmarks of pathogenicity determinants. On the basis of these observations, we propose that the general use of DNA-damaging agents coupled with differential gene expression analysis may be a useful and easy method for identifying pathogenicity determinants in diverse organisms.
Enterococcus faecalis
V583 Contains a Cytochrome
bd
-Type Respiratory Oxidase
Authors: Winstedt Lena , Frankenberg Lena , Hederstedt Lars , von Wachenfeldt Claes 
Published: July 2002

ABSTRACT

We have cloned an
Enterococcus faecalis
gene cluster,
cydABCD
, which when expressed in
Bacillus subtilis
results in a functional cytochrome
bd
terminal oxidase. Our results indicate that
E. faecalis
V583 cells have the capacity of aerobic respiration when grown in the presence of heme.
The Mitochondrial Alcohol Dehydrogenase Adh3p Is Involved in a Redox Shuttle inSaccharomyces cerevisiae
Authors: Bakker Barbara M. , Bro Christoffer , Kötter Peter , Luttik Marijke A. H. , van Dijken Johannes P. , Pronk Jack T. 
Published: July 2002

ABSTRACTNDI1is the unique gene encoding the internal mitochondrial NADH dehydrogenase ofSaccharomyces cerevisiae. The enzyme catalyzes the transfer of electrons from intramitochondrial NADH to ubiquinone. Surprisingly,NDI1is not essential for respiratory growth. Here we demonstrate that this is due to in vivo activity of an ethanol-acetaldehyde redox shuttle, which transfers the redox equivalents from the mitochondria to the cytosol. Cytosolic NADH can be oxidized by the external NADH dehydrogenases. Deletion ofADH3, encoding mitochondrial alcohol dehydrogenase, did not affect respiratory growth in aerobic, glucose-limited chemostat cultures. Also, anndi1Δ mutant was capable of respiratory growth under these conditions. However, when bothADH3andNDI1were deleted, metabolism became respirofermentative, indicating that the ethanol-acetaldehyde shuttle is essential for respiratory growth of thendi1Δ mutant. In anaerobic batch cultures, the maximum specific growth rate of theadh3Δ mutant (0.22 h−1) was substantially reduced compared to that of the wild-type strain (0.33 h−1). This is consistent with the hypothesis that the ethanol-acetaldehyde shuttle is also involved in maintenance of the mitochondrial redox balance under anaerobic conditions. Finally, it is shown that another mitochondrial alcohol dehydrogenase is active in theadh3Δ ndi1Δ mutant, contributing to residual redox-shuttle activity in this strain.
Overexpression of Protease-Deficient DegP
S210A
Rescues the Lethal Phenotype of
Escherichia coli
OmpF Assembly Mutants in a
degP
Background
Authors: Misra Rajeev , CastilloKeller Maria , Deng Ming 
Published: July 2002

ABSTRACT

Replacement of OmpF's conserved carboxy-terminal phenylalanine with dissimilar amino acids severely impaired its assembly into stable trimers. In some instances, interactions of mutant proteins with the outer membrane were also affected, as judged by their hypersensitivity phenotype. Synthesis of all mutant OmpF proteins elevated the expression of periplasmic protease DegP, and synthesis of most of them made its presence obligatory for cell viability. These results showed a critical role for DegP in the event of aberrant outer membrane protein assembly. The lethal phenotype of mutant OmpF proteins in a
degP
null background was eliminated when a protease-deficient DegP
S210A
protein was overproduced. Our data showed that this rescue from lethality and a subsequent increase in mutant protein levels in the envelope did not lead to the proper assembly of the mutant proteins in the outer membrane. Rather, a detergent-soluble and thermolabile OmpF species resembling monomers accumulated in the mutants, and to a lesser extent in the parental strain, when DegP
S210A
was overproduced. Interestingly, this also led to the localization of a significant amount of mutant polypeptides to the inner membrane, where DegP
S210A
also fractionated. These results suggested that the DegP
S210A
-mediated rescue from toxicity involved preferential sequestration of misfolded OmpF monomers from the normal assembly pathway.
Alternative Transcription Factor ς
B
Is Involved in Regulation of Biofilm Expression in a
Staphylococcus aureus
Mucosal Isolate
Authors: Rachid Shwan , Ohlsen Knut , Wallner Ursula , Hacker Jörg , Hecker Michael , Ziebuhr Wilma 
Published: July 2002

ABSTRACT

Osmotic stress was found to induce biofilm formation in a
Staphylococcus aureus
mucosal isolate. Inactivation of a global regulator of the bacterial stress response, the alternative transcription factor ς
B
, resulted in a biofilm-negative phenotype and loss of salt-induced biofilm production. Complementation of the mutant strain with an expression plasmid encoding ς
B
completely restored the wild-type phenotype. The combined data suggest a critical role of ς
B
in
S. aureus
biofilm regulation under environmental stress conditions.