bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal Immunization of Mice with Group B Streptococcal Protein Rib and Cholera Toxin B Subunit Confers Protection against Lethal Infection
Authors: Larsson Charlotte , Holmgren Jan , Lindahl Gunnar , Bergquist Charlotta 
Published: January 2004

ABSTRACT
Intranasal immunization of mice with Rib, a cell surface protein of group B streptococcus (GBS), conjugated to or simply coadministered with the recombinant cholera toxin B subunit, induces systemic immunoglobulin G (IgG) and local IgA antibody responses and confers protection against lethal GBS infection. These findings have implications for the development of a human GBS vaccine.
Downregulation of the DNA-Binding Activity of Nuclear Factor-κB p65 Subunit in
Porphyromonas gingivalis
Fimbria-Induced Tolerance
Authors: Hajishengallis George , Genco Robert J. 
Published: January 2004

ABSTRACT

Porphyromonas gingivalis
fimbriae induce high levels of nuclear factor-κB (NF-κB)-dependent cytokine release upon primary but not secondary stimulation of monocytic cells (FimA tolerance). In this study, fimbriae induced Toll-like receptor-mediated activation of both p50 and p65 subunits of NF-κB upon primary cellular activation. However, activation of the transactivating p65 subunit (but not of the transcriptionally inactive p50 subunit) was significantly inhibited in fimbria-restimulated cells. Moreover, expression of a NF-κB-dependent reporter gene was inhibited upon secondary stimulation with fimbriae. NF-κB p65 downregulation may thus contribute to induction of FimA tolerance.
Hydrogen Peroxide-Mediated Killing of
Caenorhabditis elegans
: a Common Feature of Different Streptococcal Species
Authors: Bolm Maike , Jansen Wouter T. M. , Schnabel Ralf , Chhatwal Gursharan S. 
Published: January 2004

ABSTRACT

Recently, we reported that
Streptococcus pyogenes
kills
Caenorhabditis elegans
by the use of hydrogen peroxide (H
2
O
2
). Here we show that diverse streptococcal species cause death of
C. elegans
larvae in proportion to the level of H
2
O
2
produced. H
2
O
2
may mask the effects of other pathogenicity factors of catalase-negative bacteria in the
C. elegans
infection model.
Identification of Five Outer Membrane-Associated Proteins among Cross-Protective Factor Proteins ofPasteurella multocida
Authors: Tabatabai Louisa B. , Zehr Emilie S. 
Published: January 2004

ABSTRACTFowl cholera is caused byPasteurella multocidaserovars A:1, A:3, and A:4. The 39-kDa cross-protective factor protein and four other membrane proteins of the membrane proteome ofP. multocidawere identified. We determined that the 39-kDa cross-protective protein wasPasteurellalipoprotein B, or PlpB.
Comparison of
Campylobacter jejuni
Isolates Implicated in Guillain-Barré Syndrome and Strains That Cause Enteritis by a DNA Microarray
Authors: Leonard Edward E. , Tompkins Lucy S. , Falkow Stanley , Nachamkin Irving 
Published: January 2004

ABSTRACT

We asked whether
Campylobacter jejuni
isolated from patients with Guillain-Barré syndrome (GBS) differ from isolates isolated from patients with uncomplicated gastrointestinal infection using DNA microarray analysis. We found that specific GBS genes or regions were not identified, and microarray analysis confirmed significant genomic heterogeneity among the isolates.
Haemophilus influenzaePorin Induces Toll-Like Receptor 2-Mediated Cytokine Production in Human Monocytes and Mouse Macrophages
Authors: Galdiero Marilena , Galdiero Massimiliano , Finamore Emiliana , Rossano Fabio , Gambuzza Maria , Catania Maria Rosaria , Teti Giuseppe , Midiri Angelina , Mancuso Giuseppe 
Published: January 2004

ABSTRACTThe production of proinflammatory cytokines is likely to play a major pathophysiological role in meningitis and other infections caused byHaemophilus influenzaetype b (Hib). Previous studies have shown that Hib porin contributes to signaling of the inflammatory cascade. We examined here the role of Toll-like receptors (TLRs) and the TLR-associated adaptor protein MyD88 in Hib porin-induced production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Hib porin-induced TNF-α and IL-6 production was virtually eliminated in macrophages from TLR2- or MyD88-deficient mice. In contrast, macrophages from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, which are defective in TLR4 function, responded normally to Hib porin. Moreover anti-TLR2 antibodies but not anti-TLR4 antibodies significantly reduced Hib porin-stimulated TNF-α and IL-6 release from the human monocytic cell line THP-1. These data indicate that the TLR2/MyD88 pathway plays an essential role in Hib porin-mediated cytokine production. These findings may be useful in the development of alternative therapies aimed at reducing excessive inflammatory responses during Hib infections.
The Bacterial Insertion Sequence Element IS
256
Occurs Preferentially in Nosocomial
Staphylococcus epidermidis
Isolates: Association with Biofilm Formation and Resistance to Aminoglycosides
Authors: Kozitskaya Svetlana , Cho Seung-Hak , Dietrich Katja , Marre Reinhard , Naber Kurt , Ziebuhr Wilma 
Published: January 2004

ABSTRACT

Staphylococcus epidermidis
is a normal constituent of the healthy human microflora, but it is also the most common cause of nosocomial infections associated with the use of indwelling medical devices. Isolates from device-associated infections are known for their pronounced phenotypic and genetic variability, and in this study we searched for factors that might contribute to this flexibility. We show that mutator phenotypes, which exhibit elevated spontaneous mutation rates, are rare among both pathogenic and commensal
S. epidermidis
strains. However, the study revealed that, in contrast to those of commensal strains, the genomes of clinical
S. epidermidis
strains carry multiple copies of the insertion sequence IS
256
, while other typical staphylococcal insertion sequences, such as IS
257
and IS
1272
, are distributed equally among saprophytic and clinical isolates. Moreover, detection of IS
256
was found to be associated with biofilm formation and the presence of the
icaADBC
operon as well as with gentamicin and oxacillin resistance in the clinical strains. The data suggest that IS
256
is a characteristic element in the genome of multiresistant nosocomial
S. epidermidis
isolates that might be involved in the flexibility and adaptation of the genome in clinical isolates.
The Siderophore Receptor IroN, but Not the High-Pathogenicity Island or the Hemin Receptor ChuA, Contributes to the Bacteremic Step of
Escherichia coli
Neonatal Meningitis
Authors: Nègre Valérie Lefranc , Bonacorsi Stéphane , Schubert Soren , Bidet Philippe , Nassif Xavier , Bingen Edouard 
Published: January 2004

ABSTRACT

Using a neonatal rat meningitis model, we examined the involvement of three iron uptake systems, namely, the high-pathogenicity island, the hemin receptor ChuA, and the siderophore receptor IroN, in the pathogenesis of
Escherichia coli
neonatal meningitis. Only IroN appeared to play a major role during the bacteremic step of the disease.
Contribution of CsrR-Regulated Virulence Factors to the Progress and Outcome of Murine Skin Infections byStreptococcus pyogenes
Authors: Engleberg N. Cary , Heath Andrew , Vardaman Kristal , DiRita Victor J. 
Published: January 2004

ABSTRACTStreptococcus pyogeneswith null mutations in thecsrRSregulatory locus are highly virulent in mice due to derepression of hyaluronic acid capsule synthesis and exotoxins, e.g., streptolysin S (SLS) and pyrogenic exotoxin B (SpeB). We generated derivatives of a ΔcsrRSstrain that also carry deletions inhasAB(leading to an acapsular phenotype) or insagA(phenotypically SLS−) or an interruption ofspeB(SpeB−) to test the relative contributions of these factors to the development of necrotic skin lesions. Inoculation of 2 × 106to 4 × 106CFU of either acapsular or SLS−strains into hairless mice resulted in lesions ∼70% smaller than those of the ΔcsrRSparent strain. Elimination of SLS also reduced lethality from 100% to 0% at this inoculum (P< 10−7; Fisher exact test). In contrast, SLS+SpeB−mutants yielded lesions that were only 41% smaller than the parent strain (t= 2.2;P= 0.04), but only 3 the 17 lesions had dermal sloughing (P= 10−5). The nonulcerative lesions associated with SpeB−strains appeared pale with surrounding erythema. We conclude that capsule and SLS contribute to the subcutaneous spread ofS. pyogenesand to a fatal outcome of infection. SpeB facilitates early dermal ulceration but has minor influence on lesion size and mortality. Large ulcerative lesions are observed only when both toxins are present.
Role of B7 Costimulatory Molecules in Immune Responses and T-Helper Cell Differentiation in Response to Recombinant HagB fromPorphyromonas gingivalis
Authors: Zhang Ping , Martin Michael , Yang Qiu-Bo , Michalek Suzanne M. , Katz Jannet 
Published: January 2004

ABSTRACTIn addition to antigen-specific signals mediated through the T-cell receptor, T cells also require antigen nonspecific costimulation for activation. The B7 family of molecules on antigen-presenting cells, which include B7-1 (CD80) and B7-2 (CD86), play important roles in providing costimulatory signals required for development of antigen-specific immune responses. Hemagglutinin B (HagB) is a nonfimbrial adhesin of the periodontopathic microorganismPorphyromonas gingivalisand is thought to be involved in the attachment of the bacterium to host tissues. However, the immune mechanisms involved in responses to HagB and their roles in pathogenesis have yet to be elucidated. Therefore, the purpose of this study was to determine the role of B7 costimulatory molecules on T-helper-cell differentiation for the induction of immune responses to HagB. Mice deficient in either or both of the costimulatory molecules B7-1 and B7-2 were used to explore their role in immune responses to HagB after subcutaneous immunization. B7-1−/−mice had levels of immunoglobulin G (IgG) anti-HagB antibody activity in serum similar to those of wild-type mice, whereas lower serum IgG anti-HagB antibody responses were seen in B7-2−/−mice. Moreover, significantly lower numbers of IgG antibody-secreting cells and lower levels of CD4+-T-cell proliferation were observed in B7-2−/−mice compared to wild-type mice. No serum IgG response to HagB was detected in B7-1/B7-2−/−mice. Analysis of the subclass of the serum IgG responses and the cytokines induced in response to HagB revealed that B7-2−/−mice had significantly lower IgG1 and higher IgG2a anti-HagB antibody responses compared to wild-type mice. The B7-2−/−mice also had significantly reduced levels of interleukin-4 (IL-4) and IL-5 and enhanced level of gamma interferon. Furthermore, assessment of B7-1 and B7-2 expression on B cells and macrophages derived from wild-type BALB/c mice after in vitro stimulation with HagB revealed a predominant upregulation in the expression of the B7-2 costimulatory molecule on B cells and macrophages. Essentially no change was seen in the expression of B7-1. Taken together, these results suggest a critical role for B7, especially B7-2, for the preferential induction of a Th2-like response to HagB.
Surfactant Protein A Modulates the Inflammatory Response in Macrophages during Tuberculosis
Authors: Gold Jeffrey A. , Hoshino Yoshihiko , Tanaka Naohiko , Rom William N. , Raju Bindu , Condos Rany , Weiden Michael D. 
Published: January 2004

ABSTRACTTuberculosis leads to immune activation and increased human immunodeficiency virus type 1 (HIV-1) replication in the lung. However, in vitro models of mycobacterial infection of human macrophages do not fully reproduce these in vivo observations, suggesting that there are additional host factors. Surfactant protein A (SP-A) is an important mediator of innate immunity in the lung. SP-A levels were assayed in the human lung by using bronchoalveolar lavage (BAL). There was a threefold reduction in SP-A levels during tuberculosis only in the radiographically involved lung segments, and the levels returned to normal after 1 month of treatment. The SP-A levels were inversely correlated with the percentage of neutrophils in BAL fluid, suggesting that low SP-A levels were associated with increased inflammation in the lung. Differentiated THP-1 macrophages were used to test the effect of decreasing SP-A levels on immune function. In the absence of infection withMycobacterium tuberculosis, SP-A at doses ranging from 5 to 0.01 μg/ml inhibited both interleukin-6 (IL-6) production and HIV-1 long terminal repeat (LTR) activity. In macrophages infected withM. tuberculosis, SP-A augmented both IL-6 production and HIV-1 LTR activity. To better understand the effect of SP-A, we measured expression of CAAT/enhancer binding protein beta (C/EBPβ), a transcription factor central to the regulation of IL-6 and the HIV-1 LTR. In macrophages infected withM. tuberculosis, SP-A reduced expression of a dominant negative isoform of C/EBPβ. These data suggest that SP-A has pleiotropic effects even at the low concentrations found in tuberculosis patients. This protein augments inflammation in the presence of infection and inhibits inflammation in uninfected macrophages, protecting uninvolved lung segments from the deleterious effects of inflammation.
Porphyromonas gingivalis
Genes Involved in
fimA
Regulation
Authors: Xie Hua , Kozlova Natalia , Lamont Richard J. 
Published: January 2004

ABSTRACT

Porphyromonas gingivalis
is an important component of the complex plaque biofilm that is a direct precursor of periodontal disease. The major fimbriae are required for attachment to oral surfaces and are an important virulence factor. Fimbrillin (FimA) expression in
P. gingivalis
is inhibited by surface molecule of
Streptococcus cristatus
, an early colonizer of dental plaque. In this study, differential display PCR was used to identify
P. gingivalis
genes that are regulated in response to
S. cristatus
. Of several differentially expressed genes,
pg2131
and
pg2167
were upregulated by
S. cristatus
signaling molecules. A null mutant of
pg2167
did not transcriptionally regulate
fimA
following exposure to
S. cristatus
. In fact,
fimA
transcription was enhanced in the
pg2167
mutant, suggesting that
pg2167
may act to repress
fimA
expression. In contrast, a mutation in
pg2131
did not affect transcription of
fimA
in the presence of
S. cristatus
. However, production of fimbrillin was significantly diminished in the
pg2131
mutant, implicating involvement in posttranscriptional regulation in fimbriation. These data suggest that
P. gingivalis
fimbriation is controlled by more than one regulation mechanism, involving both transcriptional and posttranscriptional processes.
Release of a Potent Polymorphonuclear Leukocyte Chemoattractant Is Regulated by White-Opaque Switching inCandida albicans
Authors: Geiger Jeremy , Wessels Deborah , Lockhart Shawn R. , Soll David R. 
Published: January 2004

ABSTRACTPrevious studies employing transmembrane assays suggested thatCandida albicansand related species, as well asSaccharomyces cerevisiae, release chemoattractants for human polymorphonuclear leukocytes (PMNs). Because transmembrane assays do not definitively distinguish between chemokinesis and chemotaxis, single-cell chemotaxis assays were used to confirm these findings and test whether mating-type or white-opaque switching affects the release of attractant. Our results demonstrate thatC. albicans,C. dubliniensis,C. tropicalis,C. parapsilosis, andC. glabratarelease bona fide chemoattractants for PMNs.S. cerevisiae, however, releases a chemokinetic factor but not a chemoattractant. Characterization of theC. albicanschemoattractant revealed that it is a peptide of approximately 1 kDa. Whereas the mating type ofC. albicansdid not affect the release of chemoattractant, switching did. White-phase cells released chemoattractant, but opaque-phase cells did not. Since the opaque phase ofC. albicansrepresents the mating-competent phenotype, it may be that opaque-phase cells selectively suppress the release of chemoattractant to facilitate mating.
Patterns of Variations in
Escherichia coli
Strains That Produce Cytolethal Distending Toxin
Authors: Pickett Carol L. , Lee Robert B. , Eyigor Aysegul , Elitzur Ben , Fox Emily M. , Strockbine Nancy A. 
Published: January 2004

ABSTRACT

A collection of 20
Escherichia coli
strains that produce cytolethal distending toxin (CDT) were analyzed for their virulence-associated genes. All of these strains were serotyped, and multiplex PCR analysis was used to ascertain the presence of genes encoding other virulence factors, including Shiga toxin, intimin, enterohemolysin, cytotoxic necrotizing factor type 1 (CNF1) and CNF2, heat-stable toxin, and heat-labile toxin. These CDT-producing strains possessed various combinations of known virulence genes, some of which have not been noted before. Partial
cdtB
sequences were obtained from 10 of these strains, and their predicted CdtB sequences were compared to known
E. coli
CdtB sequences; some of the sequences were identical to known CdtB sequences, but two were not. PCR primers based on sequence differences between the known
cdt
sequences were tested for their ability to detect CDT producers and to determine CDT type. Correlations between the type of CDT produced, the presence of other virulence properties, and overall strain relatedness revealed that the CDT producers studied here can be divided into three general groups, with distinct differences in CDT type and in their complement of virulence-associated genes.
Host Cell Contact-Induced Transcription of the Type IV Fimbria Gene Cluster of
Actinobacillus pleuropneumoniae
Authors: Boekema Bouke K. H. L. , Van Putten Jos P. M. , Stockhofe-Zurwieden Norbert , Smith Hilde E. 
Published: January 2004

ABSTRACT

Type IV pili (Tfp) of gram-negative species share many characteristics, including a common architecture and conserved biogenesis pathway. Much less is known about the regulation of Tfp expression in response to changing environmental conditions. We investigated the diversity of Tfp regulatory systems by searching for the molecular basis of the reported variable expression of the Tfp gene cluster of the pathogen
Actinobacillus pleuropneumoniae
. Despite the presence of an intact Tfp gene cluster consisting of four genes,
apfABCD
, no Tfp were formed under standard growth conditions. Sequence analysis of the predicted major subunit protein ApfA showed an atypical alanine residue at position −1 from the prepilin peptidase cleavage site in 42 strains. This alanine deviates from the consensus glycine at this position in Tfp from other species. Yet, cloning of the
apfABCD
genes under a constitutive promoter in
A. pleuropneumoniae
resulted in pilin and Tfp assembly. Tfp promoter-
luxAB
reporter gene fusions demonstrated that the Tfp promoter was intact but tightly regulated. Promoter activity varied with bacterial growth phase and was detected only when bacteria were grown in chemically defined medium. Infection experiments with cultured epithelial cells demonstrated that Tfp promoter activity was upregulated upon adherence of the pathogen to primary cultures of lung epithelial cells. Nonadherent bacteria in the culture supernatant exhibited virtually no promoter activity. A similar upregulation of Tfp promoter activity was observed in vivo during experimental infection of pigs. The host cell contact-induced and in vivo-upregulated Tfp promoter activity in
A. pleuropneumoniae
adds a new dimension to the diversity of Tfp regulation.
Two TonB Systems in
Actinobacillus pleuropneumoniae
: Their Roles in Iron Acquisition and Virulence
Authors: Beddek Amanda J. , Sheehan Brian J. , Bossé Janine T. , Rycroft Andrew N. , Kroll J. Simon , Langford Paul R. 
Published: January 2004

ABSTRACT

Iron acquisition in vivo by
Actinobacillus pleuropneumoniae
depends upon a functional TonB system. Tonpitak et al. (W. Tonpitak, S. Thiede, W. Oswald, N. Baltes, and G.-F. Gerlach, Infect. Immun.
68:
1164-1170, 2000) have described one such system, associated with
tbpBA
encoding the transferrin receptor, and here we report a second, termed
tonB2
. This gene cluster (
exbB2
-
exbD2
-
tonB2
) is highly homologous to those in other
Pasteurellaceae
, unlike the earlier system described (now termed
tonB1
), suggesting that it is the indigenous system for this organism. Both
tonB2
and
tonB1
are upregulated upon iron restriction. TonB2, but not TonB1, was found to be essential for growth in vitro when the sole source of iron was hemin, porcine hemoglobin, or ferrichrome. In the case of iron provided as iron-loaded porcine transferrin, neither
tonB
mutant was viable. The
tonB1
phenotype could be explained by a polar effect of the mutation on transcription of downstream
tbp
genes. We propose that TonB2 is crucial for the acquisition of iron provided in this form, interacting with accessory proteins of the TonB1 system that have been demonstrated to be necessary by Tonpitak et al. TonB2 appears to play a much more important role in
A. pleuropneumoniae
virulence than TonB1. In an acute porcine infection model, the
tonB2
mutant was found to be highly attenuated, while the
tonB1
mutant was not. We hypothesize that acquisition of the
tonB1-tbp
gene cluster confers a biological advantage through its capacity to utilize transferrin-iron but that TonB1 itself plays little or no part in this process.
Binding and Agglutination of
Streptococcus pneumoniae
by Human Surfactant Protein D (SP-D) Vary between Strains, but SP-D Fails To Enhance Killing by Neutrophils
Authors: Jounblat Rania , Kadioglu Aras , Iannelli Francesco , Pozzi Gianni , Eggleton Paul , Andrew Peter W. 
Published: January 2004

ABSTRACT

Recombinant human surfactant protein D (SP-D) expressed in
Escherichia coli
, consisting of the head and neck regions of the native molecule, bound to all strains of
Streptococcus pneumoniae
that were tested, but the extent of binding varied between strains of differing capsular serotypes. The recombinant protein expressed in the yeast
Pichia pastoris
did not bind. Full-length native SP-D aggregated pneumococci in a calcium-dependent manner that was inhibited by maltose acting as a competitive sugar. The ability of SP-D to modulate the uptake and killing of pneumococci by human neutrophils was also addressed. Neither recombinant truncated SP-D nor native full-length SP-D enhanced the killing of pneumococci by human neutrophils. Aggregation of pneumococci varied not only between strains of the same multilocus sequence type and different serotypes but also between strains of the same serotype. However, use of recombinant strains in which the serotype had been changed showed that the degree of aggregation was influenced by the capsular type. Indeed, a 19F serotype strain which was not aggregated by SP-D did exhibit aggregation when the original isogenic strain was capsule switched to capsular serotype 3. However, although our results show that SP-D is capable of aggregating most pneumococci, no correlation between the degree of aggregation and the capsule or multilocus sequence type of the pneumococcus was clearly apparent. Therefore, although the capsule serotype is not the only determinant of aggregation by SP-D, the data presented here indicate that it does have a role to play.