bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relapsing Fever SpirochetesBorrelia recurrentisandB. duttoniiAcquire Complement Regulators C4b-Binding Protein and Factor H
Authors: Meri T. , Cutler S. J. , Blom A. M. , Meri S. , Jokiranta T. S. 
Published: June 2006

ABSTRACTRelapsing fever is a rapidly progressive and severe septic disease caused by certainBorreliaspirochetes. The disease is divided into two forms, i.e., epidemic relapsing fever, caused byBorrelia recurrentisand transmitted by lice, and the endemic form, caused by severalBorreliaspecies, such asB. duttonii, and transmitted by soft-bodied ticks. The spirochetes enter the bloodstream by the vector bite and live persistently in plasma even after the development of specific antibodies. This leads to fever relapses and high mortality and clearly indicates that theBorreliaorganisms utilize effective immune evasion strategies. In this study, we show that the epidemic relapsing fever pathogenB. recurrentisand an endemic relapsing fever pathogen,B. duttonii, are serum resistant, i.e., resistant to complement in vitro. They acquire the host alternative complement pathway regulator factor H on their surfaces in a similar way to that of the less serum-resistant Lyme disease pathogen,B. burgdorferisensu stricto. More importantly, the relapsing fever spirochetes specifically bind host C4b-binding protein, a major regulator of the antibody-mediated classical complement pathway. Both complement regulators retained their functional activities when bound to the surfaces of the spirochetes. In conclusion, this is the first report of complement evasion byBorrelia recurrentisandB. duttoniiand the first report showing capture of C4b-binding protein by spirochetes.
CPS1
, a Homolog of the
Streptococcus pneumoniae
Type 3 Polysaccharide Synthase Gene, Is Important for the Pathobiology of
Cryptococcus neoformans
Authors: Chang Y. C. , Jong A. , Huang S. , Zerfas P. , Kwon-Chung K. J. 
Published: June 2006

ABSTRACT

The polysaccharide capsule is known to be the major factor required for the virulence of
Cryptococcus neoformans
. We have cloned and characterized a gene, designated
CPS1
, that encodes a protein containing a glycosyltransferase moiety and shares similarity with the type 3 polysaccharide synthase encoded by the
cap3B
gene of
Streptococcus pneumoniae
. Cps1p also shares similarity with hyaluronan synthase of higher eukaryotes. Deletion of the
CPS1
gene from a serotype D strain of
C. neoformans
resulted in a slight reduction of the capsule size as observed by using an India ink preparation. The growth at 37°C was impaired, and the ability to associate with human brain endothelial cells in vitro was also significantly reduced by the deletion of
CPS1
. Using site-specific mutagenesis, we showed that the conserved glycosyltransferase domains are critical for the ability of the strain to grow at elevated temperatures. A hyaluronan enzyme-linked immunosorbent assay method demonstrated that
CPS1
is important for the synthesis of hyaluronan or its related polysaccharides in
C. neoformans
. Comparisons between the wild-type and the
cps1Δ
strains, using three different transmission electron microscopic methods, indicated that the
CPS1
gene product is involved in the composition or maintenance of an electron-dense layer between the outer cell wall and the capsule. These and the virulence studies in a mouse model suggested that the
CPS1
gene is important in the pathobiology of
C. neoformans
.
Role of Calcineurin in Stress Resistance, Morphogenesis, and Virulence of a
Candida albicans
Wild-Type Strain
Authors: Bader Teresa , Schröppel Klaus , Bentink Stefan , Agabian Nina , Köhler Gerwald , Morschhäuser Joachim 
Published: June 2006

ABSTRACT

By generating a calcineurin mutant of the
Candida albicans
wild-type strain SC5314 with the help of a new recyclable dominant selection marker, we confirmed that calcineurin mediates tolerance to a variety of stress conditions but is not required for the ability of
C. albicans
to switch to filamentous growth in response to hypha-inducing environmental signals. While calcineurin was essential for virulence of
C. albicans
in a mouse model of disseminated candidiasis, deletion of
CMP1
did not significantly affect virulence during vaginal or pulmonary infection, demonstrating that the requirement for calcineurin for a successful infection depends on the host niche.
Characterization of a Novel Porin Involved in Systemic
Yersinia enterocolitica
Infection
Authors: Mildiner-Earley Shirly , Miller Virginia L. 
Published: June 2006

ABSTRACT

Yersinia enterocolitica
is an enteric pathogen capable of causing systemic disease in a murine model. We have identified a novel protein,
s
ystemic
f
actor
p
rotein A (SfpA), conserved in other pathogenic bacteria that is involved in systemic disease. Analysis of bacterial colonization revealed that a Δ
sfpA
strain is defective in mesenteric lymph node colonization. Bioinformatics and functional studies suggest that SfpA is a porin.
Alcohol Dehydrogenase Restricts the Ability of the Pathogen
Candida albicans
To Form a Biofilm on Catheter Surfaces through an Ethanol-Based Mechanism
Authors: Mukherjee Pranab K. , Mohamed Sotohy , Chandra Jyotsna , Kuhn Duncan , Liu Shuqing , Antar Omar S. , Munyon Ryan , Mitchell Aaron P. , Andes David , Chance Mark R. , Rouabhia Mahmoud , Ghannoum Mahmoud A. 
Published: June 2006

ABSTRACT

Candida
biofilms formed on indwelling medical devices are increasingly associated with severe infections. In this study, we used proteomics and Western and Northern blotting analyses to demonstrate that alcohol dehydrogenase (ADH) is downregulated in
Candida
biofilms. Disruption of
ADH1
significantly (
P
= 0.0046) enhanced the ability of
Candida albicans
to form biofilm. Confocal scanning laser microscopy showed that the
adh1
mutant formed thicker biofilm than the parent strain (210 μm and 140 μm, respectively). These observations were extended to an engineered human oral mucosa and an in vivo rat model of catheter-associated biofilm. Inhibition of
Candida
ADH enzyme using disulfiram and 4-methylpyrazole resulted in thicker biofilm (
P
< 0.05). Moreover, biofilms formed by the
adh1
mutant strain produced significantly smaller amounts of ethanol, but larger amounts of acetaldehyde, than biofilms formed by the parent and revertant strains (
P
< 0.0001), demonstrating that the effect of Adh1p on biofilm formation is mediated by its enzymatic activity. Furthermore, we found that 10% ethanol significantly inhibited biofilm formation in vitro, with complete inhibition of biofilm formation at ethanol concentrations of ≥20%. Similarly, using a clinically relevant rabbit model of catheter-associated biofilm, we found that ethanol treatment inhibited biofilm formation by
C. albicans
in vivo (
P
< 0.05) but not by
Staphylococcus
spp. (
P
> 0.05), indicating that ethanol specifically inhibits
Candida
biofilm formation. Taken together, our studies revealed that Adh1p contributes to the ability of
C. albicans
to form biofilms in vitro and in vivo and that the protein restricts biofilm formation through an ethanol-dependent mechanism. These results are clinically relevant and may suggest novel antibiofilm treatment strategies.
Intrastrain Heterogeneity of the
mgpB
Gene in
Mycoplasma genitalium
Is Extensive In Vitro and In Vivo and Suggests that Variation Is Generated via Recombination with Repetitive Chromosomal Sequences
Authors: Iverson-Cabral Stefanie L. , Astete Sabina G. , Cohen Craig R. , Rocha Eduardo P. C. , Totten Patricia A. 
Published: June 2006

ABSTRACT

Mycoplasma genitalium
is associated with reproductive tract disease in women and may persist in the lower genital tract for months, potentially increasing the risk of upper tract infection and transmission to uninfected partners. Despite its exceptionally small genome (580 kb), approximately 4% is composed of repeated elements known as MgPar sequences (MgPa repeats) based on their homology to the
mgpB
gene that encodes the immunodominant MgPa adhesin protein. The presence of these MgPar sequences, as well as
mgpB
variability between
M. genitalium
strains, suggests that
mgpB
and MgPar sequences recombine to produce variant MgPa proteins. To examine the extent and generation of diversity within single strains of the organism, we examined
mgpB
variation within
M. genitalium
strain G-37 and observed sequence heterogeneity that could be explained by recombination between the
mgpB
expression site and putative donor MgPar sequences. Similarly, we analyzed
mgpB
sequences from cervical specimens from a persistently infected woman (21 months) and identified 17 different
mgpB
variants within a single infecting
M. genitalium
strain, confirming that
mgpB
heterogeneity occurs over the course of a natural infection. These observations support the hypothesis that recombination occurs between the
mgpB
gene and MgPar sequences and that the resulting antigenically distinct MgPa variants may contribute to immune evasion and persistence of infection.
Identification, Recombinant Expression, Immunolocalization in Macrophages, and T-Cell Responsiveness of the Major Extracellular Proteins of
Francisella tularensis
Authors: Lee Bai-Yu , Horwitz Marcus A. , Clemens Daniel L. 
Published: June 2006

ABSTRACT

A safer and more effective vaccine than the previously developed live attenuated vaccine is needed for combating
Francisella tularensis
, a highly infectious bacterial pathogen. To search for potential candidates for inclusion in a new vaccine, we characterized the proteins present in the culture filtrates of a virulent recent clinical isolate and the attenuated live vaccine strain of
F. tularensis
using a proteomic approach. We identified a total of 12 proteins; among these, catalase-peroxidase was much more abundant in the culture filtrate of the virulent clinical isolate, whereas bacterioferritin was more abundant in the culture filtrate of the live vaccine strain. Streptolysin O treatment of infected human macrophages indicated that catalase-peroxidase and the heat shock protein GroEL are released intracellularly by actively growing
F. tularensis
. Mice immunized with
F. tularensis
developed significant cell-mediated immune responses to catalase-peroxidase, the heat shock protein GroEL, and bacterioferritin as measured by splenic lymphocyte proliferation and gamma interferon production. Finally, we expressed the major culture filtrate proteins that are promising vaccine candidates in
Escherichia coli
at high levels in soluble form to facilitate study of their immunobiology and potential role in vaccines.
Expression of Putative Virulence Factors of
Escherichia coli
O157:H7 Differs in Bovine and Human Infections
Authors: Rashid Rebecca A. , Tabata Tami A. , Oatley Melissa J. , Besser Thomas E. , Tarr Phillip I. , Moseley Steve L. 
Published: June 2006

ABSTRACT

Escherichia coli
O157:H7 is a commensal organism in cattle, but it is a pathogen in humans. This differential expression of virulence suggests that specific virulence factors are regulated differently in human and bovine hosts. To test this hypothesis, relative real-time reverse transcription-PCR was used to relate the expression of several putative virulence genes (
eae
,
espA
,
stx
2
,
rfbE
,
ehxA
, and
iha
) to that of the “housekeeping” gene
gnd
during natural human and experimental bovine infection with
E. coli
O157:H7. We examined these genes in fecal samples from eight humans and four calves.
iha
and
espA
were significantly more expressed in bovine infections.
rfbE
and
ehxA
appeared to be more highly expressed in human infections, though these differences did not achieve statistical significance. Our results support the hypothesis that some virulence-associated genes of O157:H7 are differentially expressed in a host-specific manner.
Blastocystis rattiInduces Contact-Independent Apoptosis, F-Actin Rearrangement, and Barrier Function Disruption in IEC-6 Cells
Authors: Puthia Manoj K. , Sio Selena W. S. , Lu Jia , Tan Kevin S. W. 
Published: June 2006

ABSTRACTBlastocystisis an enteric protozoan purportedly associated with numerous clinical cases of diarrhea, flatulence, vomiting, and other gastrointestinal symptoms. Despite new knowledge ofBlastocystiscell biology, genetic diversity, and epidemiology, its pathogenic potential remains controversial. Numerous clinical and epidemiological studies either implicate or exonerate the parasite as a cause of intestinal disease. Therefore, the aim of this study was to investigate the pathogenic potential ofBlastocystisby studying the interactions ofBlastocystis rattiWR1, an isolate of zoonotic potential, with a nontransformed rat intestinal epithelial cell line, IEC-6. Here, we report thatB. rattiWR1 induces apoptosis in IEC-6 cells in a contact-independent manner. Furthermore, we found thatB. rattiWR1 rearranges F-actin distribution, decreases transepithelial resistance, and increases epithelial permeability in IEC-6 cell monolayers. In addition, we found that the effects ofB. rattion transepithelial electrical resistance and epithelial permeability were significantly abrogated by treatment with metronidazole, an antiprotozoal drug. Our results suggest for the first time thatBlastocystis-induced apoptosis in host cells and altered epithelial barrier function might play an important role in the pathogenesis ofBlastocystisinfections and that metronidazole has therapeutic potential in alleviating symptoms associated withBlastocystis.
cDNA Microarray Analysis of Host-Pathogen Interactions in a Porcine In Vitro Model forToxoplasma gondiiInfection
Authors: Okomo-Adhiambo Margaret , Beattie Craig , Rink Anette 
Published: June 2006

ABSTRACTToxoplasma gondiiinduces the expression of proinflammatory cytokines, reorganizes organelles, scavenges nutrients, and inhibits apoptosis in infected host cells. We used a cDNA microarray of 420 annotated porcine expressed sequence tags to analyze the molecular basis of these changes at eight time points over a 72-hour period in porcine kidney epithelial (PK13) cells infected withT. gondii. A total of 401 genes with Cy3 and Cy5 spot intensities of ≥500 were selected for analysis, of which 263 (65.6%) were induced ≥2-fold (expression ratio, ≥2.0;P≤ 0.05 [ttest]) over at least one time point and 48 (12%) were significantly down-regulated. At least 12 functional categories of genes were modulated (up- or down-regulated) byT. gondii. The majority of induced genes were clustered as transcription, signal transduction, host immune response, nutrient metabolism, and apoptosis related. The expression of selected genes altered byT. gondiiwas validated by quantitative real-time reverse transcription-PCR. These results suggest that significant changes in gene expression occur in response toT. gondiiinfection in PK13 cells, facilitating further analysis of host-pathogen interactions in toxoplasmosis in a secondary host.
Molecular and Functional Characterization of a ToxR-Regulated Lipoprotein from a Clinical Isolate ofAeromonas hydrophila
Authors: Pillai Lakshmi , Sha Jian , Erova Tatiana E. , Fadl Amin A. , Khajanchi Bijay K. , Chopra Ashok K. 
Published: June 2006

ABSTRACTHuman diseases caused by species ofAeromonashave been classified into two major groups: septicemia and gastroenteritis. In this study, we reported the molecular and functional characterization of a new virulence factor, ToxR-regulated lipoprotein, or TagA, from a diarrheal isolate, SSU, ofAeromonas hydrophila. ThetagAgene ofA. hydrophilaexhibited 60% identity with that of a recently identifiedstcEgene fromEscherichia coliO157:H7, which encoded a protein (StcE) that provided serum resistance to the bacterium and prevented erythrocyte lysis by controlling classical pathway of complement activation by cleaving the complement C1-esterase inhibitor (C1-INH). We purifiedA. hydrophilaTagA as a histidine-tagged fusion protein (rTagA) fromE. coliDE3 strain using a T7 promoter-based pET30 expression vector and nickel affinity column chromatography. rTagA cleaved C1-INH in a time-dependent manner. ThetagAisogenic mutant ofA. hydrophila, unlike its corresponding wild-type (WT) or the complemented strain, was unable to cleave C1-INH, which is required to potentiate the C1-INH-mediated lysis of host and bacterial cells. We indeed demonstrated colocalization of C1-INH and TagA on the bacterial surface by confocal fluorescence microscopy, which ultimately resulted in increased serum resistance of the WT bacterium. Likewise, we delineated the role of TagA in contributing to the enhanced ability of C1-INH to inhibit the classical complement-mediated lysis of erythrocytes. Importantly, we provided evidence that thetagAmutant was significantly less virulent in a mouse model of infection (60%) than the WT bacterium at two 50% lethal doses, which resulted in 100% mortality within 48 h. Taken together, our data provided new information on the role of TagA as a virulence factor in bacterial pathogenesis. This is the first report of TagA characterization from any species ofAeromonas.
α-2,3-Sialyltransferase EnhancesNeisseria gonorrhoeaeSurvival during Experimental Murine Genital Tract Infection
Authors: Wu Hong , Jerse Ann E. 
Published: June 2006

ABSTRACTThe addition of host-derived sialic acid toNeisseria gonorrhoeaelipooligosaccharide is hypothesized to be an important mechanism by which gonococci evade host innate defenses. This hypothesis is based primarily on in vitro assays of complement-mediated and phagocytic killing. Here we report that a nonpolar α-2,3-sialyltransferase (lst) mutant ofN. gonorrhoeaewas significantly attenuated in its capacity to colonize the lower genital tract of 17-β estradiol-treated female BALB/c mice during competitive infection with the wild-type strain. Genetic complementation of thelstmutation restored recovery of the mutant to wild-type levels. Studies with B10.D2-HCoH2dH2-T18c/OSN (C5-deficient) mice showed that attenuation of thelstmutant was not due to increased sensitivity to complement-mediated bacteriolysis, a result that is consistent with recently reported host restrictions in the complement cascade. However, Lst-deficient gonococci were killed more rapidly than sialylated wild-type gonococci following intraperitoneal injection into normal mice, which is consistent with sialylation conferring protection against killing by polymorphonuclear leukocytes (PMNs). As reported for human PMNs, sialylated gonococci were more resistant to killing by murine PMNs, and sialylation led to reduced association with and induction of a weaker respiratory burst in PMNs from estradiol-treated mice. In summary, these studies suggest sialylation confers a survival advantage toN. gonorrhoeaein mice by increasing resistance to PMN killing. This report is the first direct demonstration that α-2,3-sialyltransferase contributes toN. gonorrhoeaepathogenesis in an in vivo model. This study also validates the use of experimental murine infection to study certain aspects of gonococcal pathogenesis.
Circulating γδ T Cells in Response toSalmonellaentericaSerovar Enteritidis Exposure in Chickens
Authors: Berndt Angela , Pieper Jana , Methner Ulrich 
Published: June 2006

ABSTRACTγδT cells are considered crucial to the outcome of various infectious diseases. The present study was undertaken to characterizeγδ (T-cell receptor 1+[TCR1+]) T cells phenotypically and functionally in avian immune response. Day-old chicks were orally immunized withSalmonella entericaserovar Enteritidis live vaccine orS. entericaserovar Enteritidis wild-type strain and infected using theS. entericaserovar Enteritidis wild-type strain on day 44 of life. Between days 3 and 71, peripheral blood was examined flow cytometrically for the occurrence of γδ T-cell subpopulations differentiated by the expression of T-cell antigens. Three different TCR1+cell populations were found to display considerable variation regarding CD8α antigen expression: (i) CD8α+highTCR1+cells, (ii) CD8α+dimTCR1+cells, and (iii) CD8α−TCR1+cells. While most of the CD8α+highTCR1+cells expressed the CD8αβ heterodimeric antigen, the majority of the CD8α+dimTCR1+cells were found to express the CD8αα homodimeric form. After immunization, a significant increase of CD8αα+highγδ T cells was observed within the CD8α+highTCR1+cell population. Quantitative reverse transcription-PCR revealed reduced interleukin-7 receptor α (IL-7Rα) and Bcl-x expression and elevated IL-2Rα mRNA expression of the CD8αα+highγδ T cells. Immunohistochemical analysis demonstrated a significant increase of CD8α+and TCR1+cells in the cecum and spleen and a decreased percentage of CD8β+T cells in the spleen afterSalmonellaimmunization. After infection of immunized animals, immune reactions were restricted to intestinal tissue. The study showed thatSalmonellaimmunization of very young chicks is accompanied by an increase of CD8αα+highγδ T cells in peripheral blood, which are probably activated, and thus represent an important factor for the development of a protective immune response toSalmonellaorganisms in chickens.
Baculovirus-Expressed Constructs Induce Immunoglobulin G That Recognizes VAR2CSA onPlasmodium falciparum- Infected Erythrocytes
Authors: Barfod Lea , Nielsen Morten A. , Turner Louise , Dahlbäck Madeleine , Jensen Anja T. R. , Hviid Lars , Theander Thor G. , Salanti Ali 
Published: June 2006

ABSTRACTWe raised specific antisera against recombinant VAR2CSA domains produced inEscherichia coliand in insect cells. All were reactive in enzyme-linked immunosorbent assay, but only insect cell-derived constructs induced immunoglobulin G (IgG) that was reactive with native VAR2CSA on the surface of infected erythrocytes. Our data show that five of the six VAR2CSA Duffy-binding-like domains are surface exposed and that induction of surface-reactive VAR2CSA-specific IgG depends critically upon antigen conformation. These findings have implications for the development of vaccines against pregnancy-associatedPlasmodium falciparummalaria.
Previous or Ongoing Schistosome Infections Do Not Compromise the Efficacy of the Attenuated Cercaria Vaccine
Authors: Kariuki Thomas M. , Van Dam Govert J. , Deelder André M. , Farah Idle O. , Yole Dorcas S. , Wilson R. Alan , Coulson Patricia S. 
Published: June 2006

ABSTRACTA current or previous schistosome infection might compromise the efficacy of a schistosome vaccine administered to humans. We have therefore investigated the influence of infection on vaccination, using the baboon as the model host and irradiatedSchistosoma mansonicercariae as the vaccine. Protection, determined from worm burdens in test and controls, was not diminished when vaccination was superimposed on a chronic infection, nor was it diminished when it followed a primary infection terminated by chemotherapy. Protection was also assessed indirectly based on fecal egg output and circulating antigen levels, as would be the case in human vaccine trials. In almost all instances, these methods overestimated protection, sometimes with discrepancies of >20%. The overwhelming immune response to egg deposition in infected animals made it difficult to discern a contribution from vaccination. Nevertheless, the well-documented immunomodulation of immune responses that follows egg deposition did not appear to impede the protective mechanisms elicited by vaccination with attenuated cercariae.