bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity amongHelicobacter pyloriStrains in Expression of the Outer Membrane Protein BabA
Authors: Hennig Ewa E. , Mernaugh Ray , Edl Jennifer , Cao Ping , Cover Timothy L. 
Published: May 2004

ABSTRACTThe BabA adhesin ofHelicobacter pyloriis an outer membrane protein that binds to the fucosylated Lewis b histo-blood group antigen on the surface of gastric epithelial cells. We screened a phage-displayed ScFv (single-chain fragment variable) recombinant antibody library for antibodies reactive with a recombinant BabA fragment and identified two such antibodies. Each antibody recognized an ∼75-kDa protein present in wild-typeH. pyloristrain J99 but absent from an isogenicbabAmutant strain. An immunoreactive BabA protein was detected by at least one of the antibodies in 18 (46%) of 39 different wild-typeH. pyloristrains and was detected more commonly incagA-positive strains than incagA-negative strains. Numerous amino acid polymorphisms were detected among BabA proteins expressed by different strains, with the greatest diversity occurring in the middle region of the proteins. Among the 18 strains that expressed a detectable BabA protein, there was considerable variation in the level of binding to Lewis b in vitro. Heterogeneity amongH. pyloristrains in expression of the BabA protein may be a factor that contributes to differing clinical outcomes amongH. pylori-infected humans.
A Heptosyltransferase Mutant of
Pasteurella multocida
Produces a Truncated Lipopolysaccharide Structure and Is Attenuated in Virulence
Authors: Harper Marina , Cox Andrew D. , St. Michael Frank , Wilkie Ian W. , Boyce John D. , Adler Ben 
Published: May 2004

ABSTRACT

Pasteurella multocida
is the causative agent of fowl cholera in birds. In a previous study using signature-tagged mutagenesis, we identified a mutant, AL251, which was attenuated for virulence in mice and in the natural chicken host. Sequence analysis indicated that AL251 had an insertional inactivation of the gene

waaQ
PM

, encoding a putative heptosyl transferase, required for the addition of heptose to lipopolysaccharide (LPS) (M. Harper, J. D. Boyce, I. W. Wilkie, and B. Adler, Infect. Immun. 71:5440-5446, 2003). In the present study, using mass spectrometry and nuclear magnetic resonance, we have confirmed the identity of the enzyme encoded by

waaQ
PM

as a heptosyl transferase III and demonstrated that the predominant LPS glycoforms isolated from this mutant are severely truncated. Complementation experiments demonstrated that providing a functional

waaQ
PM

gene in
trans
can restore both the LPS to its full length and growth in mice to wild-type levels. Furthermore, we have shown that mutant AL251 is unable to cause fowl cholera in chickens and that the attenuation observed is not due to increased serum sensitivity.
Interaction ofBlastomyces dermatitidis,Sporothrix schenckii, andHistoplasma capsulatumwithAcanthamoeba castellanii
Authors: Steenbergen Judith N. , Nosanchuk Joshua D. , Malliaris Stephanie D. , Casadevall Arturo 
Published: May 2004

ABSTRACTSeveral dimorphic fungi are important human pathogens, but the origin and maintenance of virulence in these organisms is enigmatic, since an interaction with a mammalian host is not a requisite for fungal survival. Recently,Cryptococcus neoformanswas shown to interact with macrophages, slime molds, and amoebae in a similar manner, suggesting that fungal pathogenic strategies may arise from environmental interactions with phagocytic microorganisms. In this study, we examined the interactions of three dimorphic fungi with the soil amoebaAcanthameobae castellanii. Yeast forms ofBlastomyces dermatitidis,Sporothrix schenckii, andHistoplasma capsulatumwere each ingested by amoebae and macrophages, and phagocytosis of yeast cells resulted in amoeba death and fungal growth.H. capsulatumconidia were also cytotoxic to amoebae. For each fungal species, exposure of yeast cells to amoebae resulted in an increase in hyphal cells. Exposure of an avirulent laboratory strain ofH. capsulatumtoA. castellaniiselected for, or induced, a phenotype ofH. capsulatumthat caused a persistent murine lung infection. These results are consistent with the view that soil amoebae may contribute to the selection and maintenance of certain traits in pathogenic dimorphic fungi that confer on these microbes the capacity for virulence in mammals.
Somatic Hypermutation and Diverse Immunoglobulin Gene Usage in the Human Antibody Response to the Capsular Polysaccharide of Streptococcus pneumoniaeType 6B
Authors: Zhou Jianhui , Lottenbach Kathleen R. , Barenkamp Stephen J. , Reason Donald C. 
Published: May 2004

ABSTRACTCombinatorial cloning and expression library analysis were used to determine the expressed human antibody repertoire specific for the capsular polysaccharide (PS) ofStreptococcus pneumoniaeserotype 6B. Sequence analysis of 55 6B-specific antibody Fab fragments isolated from six vaccinated donors reveal that different individuals used a variety of heavy and light chain germ line variable (V) region genes to form pneumococcal capsular PS (PPS) 6B-specific paratopes. Within each donor, however, the response was more restricted, with five of the six donors using at most one or two gene pairs to form combining sites. Analysis also indicated that although the response in each donor was oligoclonal in terms of variable gene usage, the combination of extensive somatic hypermutation, deletion of germ line-encoded residues, insertion of non-germ line-encoded residues, and intraclonal isotype switching generated a surprising degree of paratope diversity within the individuals analyzed. In contrast to previously studied PS-specific responses, we find that the PPS 6B repertoire makes use of a diverse collection of heavy-chain and light-chain V region gene products to form specific paratopes, with no apparent tendency for conservation of immunoglobulin gene usage between individuals.
Specific In Vivo Deletion of B-Cell Subpopulations Expressing Human Immunoglobulins by the B-Cell Superantigen Protein L
Authors: Viau Muriel , Longo Nancy S. , Lipsky Peter E. , Björck Lars , Zouali Moncef 
Published: May 2004

ABSTRACTSome pathogens have evolved to produce proteins, called B-cell superantigens, that can interact with human immunoglobulin variable regions, independently of the combining site, and activate B lymphocytes that express the target immunoglobulins. However, the in vivo consequences of these interactions on human B-cell numbers and function are largely unknown. Using transgenic mice expressing fully human immunoglobulins, we studied the consequences of in vivo exposure of protein L ofPeptostreptococcus magnuswith human immunoglobulins. In the mature pool of B cells, protein L exposure resulted in a specific reduction of splenic marginal-zone B cells and peritoneal B-1 cells. Splenic B cells exhibited a skewed light-chain repertoire consistent with the capacity of protein L to bind specific kappa gene products. Remarkably, these two B-cell subsets are implicated in innate B-cell immunity, allowing rapid clearance of pathogens. Thus, the present study reveals a novel mechanism that may be used by some infectious agents to subvert a first line of the host's immune defense.
Role of CD8
+
and CD4
+
T Lymphocytes in Jejunal Mucosal Injury during Murine Giardiasis
Authors: Scott Kevin G.-E. , Yu Linda C. H. , Buret André G. 
Published: May 2004

ABSTRACT

T-cell-mediated pathogenesis has been documented in various idiopathic and microbially induced intestinal disorders. Diffuse microvillous shortening seen in giardiasis is responsible for disaccharidase insufficiencies and malabsorption of electrolytes, nutrients, and water. Other mucosal changes include crypt hyperplasia and increased numbers of intraepithelial lymphocytes (IEL). A recent report using an athymic mouse model of infection showed that these epithelial injuries were dependent on T cells. The aim of the present study was to identify which subset of superior mesenteric lymph node (SMLN) T cells were responsible for mucosal alterations in giardiasis. CD4
+
and CD8
+
T cells, as well as whole lymphocyte populations, were isolated from SMLN of
Giardia muris
-infected mice for adoptive transfer. Jejunal segments of recipient mice were assessed for brush border ultrastructure, sucrase activity, crypt/villus ratio, and IEL numbers. Mice that received enriched CD8
+
and whole SMLN lymphocytes, but not CD4
+
T cells, from infected donors showed diffuse shortening of microvilli, loss of brush border surface area, impaired sucrase activity, and increased crypt/villus ratios compared to respective controls. Transfer of whole SMLN lymphocytes, as well as enriched CD4
+
or CD8
+
T cells, from infected donors led to increased IEL numbers in the recipient jejunum. The findings indicate that loss of intestinal brush border surface area, reduced disaccharidase activities, and increased crypt/villus ratios in giardiasis are mediated by CD8
+
T cells, whereas both CD8
+
and CD4
+
SMLN T cells regulate the influx of IEL.
Helicobacter pyloriActivates the Early Growth Response 1 Protein in Gastric Epithelial Cells
Authors: Abdel-Latif M. M. M. , Windle H. J. , Fitzgerald K. A. , Ang Y. S. , Eidhin D. Ní , Li-Weber M. , Sabra K. , Kelleher D. 
Published: May 2004

ABSTRACTThe early growth response 1 (Egr-1) transcription factor is rapidly induced by various stimuli and is implicated in the regulation of cell growth, differentiation, and gene expression. The aim of this study was to examine the effect ofHelicobacter pylorion the expression of Egr-1 and Egr-1-regulated genes in gastric epithelial AGS cells. Egr-1 expression was assayed by immunoblotting and electrophoretic mobility shift assays usingH. pylori-stimulated AGS cells. Transient transfection experiments with promoter-reporter constructs of CD44, ICAM-1, and CD95L were used for expression studies.H. pyloriinduced the expression of Egr-1 in gastric epithelial cell lines in a dose-dependent manner, with the rapid kinetics that are typical of this class of transcription factors. Immunohistochemical studies of biopsies revealed that Egr-1 expression is more abundant inH. pylori-positive patients than in uninfected individuals. Reporter-promoter transfection studies indicated that Egr-1 binding is required for theH. pylori-induced transcriptional promoter activity of the CD44, ICAM-1, and CD95L (APO-1/Fas) constructs. The blocking ofegr-1with an antisense sequence preventedH. pylori-induced Egr-1 and CD44 protein expression. The MEK1/2 signaling cascade participates inH. pylori-mediated Egr-1 expression, but the p38 pathway does not. The data indicate thatH. pyloriinduces Egr-1 expression in AGS cells in vitro and that the Egr-1 protein is readily detectable in biopsies fromH. pylori-positive subjects. These observations suggest thatH. pylori-associated Egr-1 expression may play a role, in part, inH. pylori-induced pathology.
Protective Role of Interleukin-6 duringYersinia enterocoliticaInfection Is Mediated through the Modulation of Inflammatory Cytokines
Authors: Dube Peter H. , Handley Scott A. , Lewis James , Miller Virginia L. 
Published: May 2004

ABSTRACTYersinia enterocoliticais a gram-negative enteric pathogen responsible for a number of gastrointestinal disorders. A striking feature of the pathology of aY. enterocoliticainfection is inflammation. Recently, we demonstrated a role for interleukin-1α (IL-1α) in the establishment of intestinal inflammation in response to aY. enterocoliticainfection. A cytokine directly affected by IL-1 levels is IL-6. A previous report suggested that IL-6 plays an anti-inflammatory role duringY. enterocoliticainfection, and in other systems IL-6 has been shown to be proinflammatory. Therefore, a closer examination of the roles of IL-6 and inflammatory cytokines in the control ofY. enterocoliticainfection in IL-6−/−mice was undertaken.Y. enterocoliticaorganisms were more virulent in the IL-6−/−mice (60-fold decreased 50% lethal dose) and colonized systemic tissues more rapidly and to a higher level than in the wild-type mice. One role of IL-6 during aY. enterocoliticainfection may be the downmodulation of the inflammatory response. The IL-6−/−mice have a more robust TH1 T-cell response, as well as hyperinflammatory pathologies. These phenotypes appear to be due to the misregulation of tumor necrosis factor alpha, monocyte chemotactic protein 1, IL-10, transforming growth factor β1, and gamma interferon in the IL-6−/−mouse. These data provide further insight into the intricate cytokine signaling pathways involved in the regulation of inflammatory responses and the control of bacterial infections.
Infection withToxoplasma gondiiIncreases Atherosclerotic Lesion in ApoE-Deficient Mice
Authors: Portugal Luciane R. , Fernandes Luciana R. , Cesar Giovana C. , Santiago Helton C. , Oliveira Dirce R. , Silva Neide M. , Silva Andrea A. , Lannes-Vieira Joseli , Arantes Rosa M. E. , Gazzinelli Ricardo T. , Alvarez-Leite Jacqueline I. 
Published: May 2004

ABSTRACTToxoplasma gondiiis an intracellular protozoan that elicits a potent inflammatory response during the acute phase of infection. Herein, we evaluate whetherT. gondiiinfection alters the natural course of aortic lesions. ApoE knockout mice were infected withT. gondii, and at 5 weeks of infection, serum, feces, and liver cholesterol; aortic lesion size, cellularity, and inflammatory cytokines; and levels of serum nitrite and gamma interferon (IFN-γ) were analyzed. Our results showed that serum cholesterol and atherogenic lipoproteins were reduced afterT. gondiiinfection. The reduction of serum levels of total cholesterol and atherogenic lipoproteins was associated with increases in the aortic lesion area, numbers of inflammatory cells, and expression of monocyte chemoattractant protein 1 and inducible nitric oxide synthase mRNA in the site of lesions as well as elevated concentrations of IFN-γ and nitrite in sera ofT. gondii-infected animals. These results suggest that infection withT. gondiiaccelerates atherosclerotic development by stimulating the proinflammatory response and oxidative stress, thereby increasing the area of aortic lesion.
TheVibrio choleraeToxR-Regulated Porin OmpU Confers Resistance to Antimicrobial Peptides
Authors: Mathur Jyoti , Waldor Matthew K. 
Published: May 2004

ABSTRACTBPI (bactericidal/permeability-increasing) is a potent antimicrobial protein that was recently reported to be expressed as a surface protein on human gastrointestinal tract epithelial cells. In this study, we investigated the resistance ofVibrio cholerae, a small-bowel pathogen that causes cholera, to a BPI-derived peptide, P2. Unlike inEscherichia coliandSalmonella entericaserovar Typhimurium, resistance to P2 inV. choleraewas not dependent on the BipA GTPase. Instead, we found that ToxR, the master regulator ofV. choleraepathogenicity, controlled resistance to P2 by regulating the production of the outer membrane protein OmpU. BothtoxRandompUmutants were at least 100-fold more sensitive to P2 than were wild-type cells. OmpU also conferred resistance to polymyxin B sulfate, suggesting that this porin may impart resistance to cationic antibacterial proteins via a common mechanism. Studies of stationary-phase cells revealed that the ToxR-repressed porin OmpT may also contribute to P2 resistance. Finally, although the mechanism of porin-mediated resistance to antimicrobial peptides remains elusive, our data suggest that the BPI peptide sensitivity of OmpU-deficientV. choleraeis not attributable to a generally defective outer membrane.
Role of HtrA in the Virulence and Competence of
Streptococcus pneumoniae
Authors: Ibrahim Yasser Musa , Kerr Alison R. , McCluskey Jackie , Mitchell Tim J. 
Published: May 2004

ABSTRACT

HtrA is a major virulence factor of
Streptococcus pneumoniae
(the pneumococcus). Deletion of the gene for HtrA from strain D39 of the pneumococcus completely abolished its virulence in mouse models of pneumonia and bacteremia, while the virulence of a second strain (TIGR4) was dramatically reduced. HtrA-negative mutants induced much less inflammation in the lungs during pneumonia than the wild type. HtrA is involved in the ability of the pneumococcus to grow at high temperatures, to resist oxidative stress, and to undergo genetic transformation. The expression and cellular location of several known virulence factors of the pneumococcus were not affected by the lack of HtrA.
Legionella dumoffiiDjlA, a Member of the DnaJ Family, Is Required for Intracellular Growth
Authors: Ohnishi Hiroko , Mizunoe Yoshimitsu , Takade Akemi , Tanaka Yoshitaka , Miyamoto Hiroshi , Harada Mine , Yoshida Shin-ichi 
Published: May 2004

ABSTRACTLegionella dumoffiiis one of the common causes of Legionnaires' disease and is capable of replicating in macrophages. To understand the mechanism of survival within macrophages, transposon mutagenesis was employed to isolate the genes necessary for intracellular growth. We identified four defective mutants after screening 790 transposon insertion mutants. Two transposon insertions were in genes homologous toicmBordotC, withindot/icmloci, required for intracellular multiplication ofL. pneumophila. The third was in a gene whose product is homologous to the 17-kDa antigen forming part of the VirB/VirD4 type IV secretion system ofBartonella henselae. The fourth was in thedjlA(for “dnaj-likeA”) gene. DjlA is a member of the DnaJ/Hsp40 family. Transcomplementation of thedjlAmutant restored the parental phenotype in J774 macrophages, A549 human alveolar epithelial cells, and the amoebaAcanthamoeba culbertsoni. Using confocal laser-scanning microscopy and transmission electron microscopy, we revealed that in contrast to the wild-type strain,L. dumoffii djlAmutant-containing phagosomes were unable to inhibit phagosome-lysosome fusion. Transmission electron microscopy also showed that in contrast to the virulent parental strain, thedjlAmutant was not able to recruit host cell rough endoplasmic reticulum. Furthermore, the stationary-phaseL. dumoffii djlAmutants were more susceptible to H2O2, high osmolarity, high temperature, and low pH than was their parental strain. These results indicate that DjlA is required for intracellular growth and organelle trafficking, as well as bacterial resistance to environmental stress. This is the first report demonstrating that a single DjlA-deficient mutant exhibits a distinct phenotype.
Identification of a Compensatory Mutant (
lpg2
−
REV
) of
Leishmania major
Able To Survive as Amastigotes within Macrophages without
LPG2
-Dependent Glycoconjugates and Its Significance to Virulence and Immunization Strategies
Authors: Späth Gerald F. , Lye Lon-Fye , Segawa Hiroaki , Turco Salvatore J. , Beverley Stephen M. 
Published: May 2004

ABSTRACT

Different
Leishmania
species rely to different extents on abundant glycoconjugates, such as lipophosphoglycan (LPG) and related molecules, in mammalian infections. Previously, we showed that
Leishmania major
deletion mutants lacking the Golgi GDP-mannose transporter
LPG2
, which is required for assembly of the dominant phosphoglycan (PG) repeats of LPG, were unable to survive in macrophages. These
lpg2
−
mutants, however, retained the ability to generate asymptomatic, persistent infections in mice. In contrast, Ilg and colleagues showed that
Leishmania mexicana LPG2
mutants retained virulence for mice. Here we identified a partial revertant population of the
L. major lpg2
−
mutants (designated
lpg2
−
REV
) that had regained the ability to replicate in macrophages and induce disease pathology through a compensatory change. Like the
lpg2
parent, the
lpg2
−
REV
revertant was unable to synthesize
LPG2
-dependent PGs in the promastigote stage and thus remained highly attenuated in the ability to induce infection. However, after considerable delay
lpg2
−
REV
revertant-infected mice exhibited lesions, and amastigotes isolated from these lesions were able to replicate within macrophages despite the fact that they were unable to synthesize PGs. Thus, in some respects, the
lpg2
−
REV
amastigotes resemble
L. mexicana
amastigotes. Future studies of the gene(s) responsible may shed light on the mechanisms employed by
L. major
to survive in the absence of
LPG2
-dependent glycoconjugates and may also improve the potential of the
lpg2
−
L. major
line to serve as a live parasite vaccine by overcoming its tendency to revert toward virulence.
Contribution of Gelatinase, Serine Protease, and
fsr
to the Pathogenesis of
Enterococcus faecalis
Endophthalmitis
Authors: Engelbert Michael , Mylonakis Eleftherios , Ausubel Frederick M. , Calderwood Stephen B. , Gilmore Michael S. 
Published: May 2004

ABSTRACT

Gelatinase and serine protease were found to contribute in concert to pathogenesis in a rabbit model of endophthalmitis. However, a mutant defective in the
fsr
regulator was observed to be more attenuated than a mutant rendered defective in the expression of gelatinase and serine protease as the result of a polar transposon insertion into the former. This increased attenuation suggests that there are possible additional pleiotropic effects of the defect in
fsr
on expression of traits contributing to the pathogenesis of enterococcal infection.
Induction of De Novo Subcortical Actin Filament Assembly by
Treponema denticola
Major Outer Sheath Protein
Authors: Amin Mohsen , Ho Andy C. S. , Lin Jenny Y. , Batista da Silva Andre Paes , Glogauer Michael , Ellen Richard P. 
Published: May 2004

ABSTRACT

Treponema denticola
and its major outer sheath protein (Msp) induce actin reorganization in fibroblasts. We adapted a barbed-end labeling/imaging assay to monitor Msp-induced subcortical actin filament assembly in neutrophils and fibroblasts. Msp, at an actin-reorganizing concentration, inhibited migration of these dissimilar cell types, whose cytoskeletal functions in locomotion and phagocytosis are crucial for immunity and healing of peripheral infections.
Porphyromonas gingivalis
RgpA and Kgp Proteinases and Adhesins Are C Terminally Processed by the Carboxypeptidase CPG70
Authors: Veith Paul D. , Chen Yu-Yen , Reynolds Eric C. 
Published: May 2004

ABSTRACT

Porphyromonas gingivalis
is a bacterial pathogen that produces the polyproteins RgpA and Kgp, which are proteolytically processed into proteinases and adhesins. We have demonstrated that the RgpA and Kgp proteinases and adhesins are C terminally processed by carboxypeptidase CPG70 by sequencing C-terminal peptides from both the wild type and an isogenic CPG70 mutant, using ion trap mass spectrometry.
Influence of Origin of Isolates, Especially Endocarditis Isolates, and Various Genes on Biofilm Formation by
Enterococcus faecalis
Authors: Mohamed Jamal A. , Huang Wenxiang , Nallapareddy Sreedhar R. , Teng Fang , Murray Barbara E. 
Published: May 2004

ABSTRACT

Endocarditis isolates of
Enterococcus faecalis
produced biofilm significantly more often than nonendocarditis isolates, and 39% of 79 versus 6% of 84 isolates produced strong biofilm (
P
< 0.0001).
esp
was not required, but its presence was associated with higher amounts of biofilm (
P
< 0.001). Mutants disrupted in
dltA
,
efaA
,
ace
,
lsa
, and six two-component regulatory systems were largely unaltered, while disruptions in
epa
,
atn
,
gelE
, and
fsr
resulted in fewer attached bacteria, as determined using phase-contrast microscopy, and less biofilm (
P
< 0.0001).
Biological Properties of Staphylococcal Enterotoxin-Like Toxin Type R
Authors: Omoe Katsuhiko , Imanishi Ken'ichi , Hu Dong-Liang , Kato Hidehito , Takahashi-Omoe Hiromi , Nakane Akio , Uchiyama Takehiko , Shinagawa Kunihiro 
Published: May 2004

ABSTRACTWe investigated the biological properties of a novel staphylococcal enterotoxin-like putative toxin, staphylococcal enterotoxin-like toxin type R (SElR). Major histocompatibility complex class II molecules were required for T-cell stimulation by SElR. SElR stimulated T cells bearing receptors Vβ 3, 11, 12, 13.2, and 14. These results suggested that SElR acts as a superantigen.