bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staphylococcus aureus
RN6390 Replicates and Induces Apoptosis in a Pulmonary Epithelial Cell Line
Authors: Kahl Barbara C. , Goulian Mark , van Wamel Willem , Herrmann Mathias , Simon Sanford M. , Kaplan Gilla , Peters Georg , Cheung Ambrose L. 
Published: July 2002

ABSTRACT

Staphylococcus aureus
frequently colonizes the airways of patients with compromised airway defenses (e.g., cystic fibrosis [CF] patients) for extended periods. Persistent and relapsing infections may be related to live
S. aureus
bacteria actively residing inside epithelial cells. In this study, we infected a respiratory epithelial cell line, which was derived from a CF patient, with
S. aureus
RN6390. Internalization of
S. aureus
was found to be time and dose dependent and could be blocked by cytochalasin D. Transmission electron microscopy revealed that internalized bacteria resided within endocytic vacuoles without any evidence of lysosomal fusion in a 24-h period. The results of internalization experiments and time-lapse fluorescence microscopy of epithelial cells infected with green fluorescent
S. aureus
indicate that, after an initial lag period of 7 to 9 h, intracellular bacteria began to replicate, with three to five divisions in a 24-h period, leading to apoptosis of infected cells. Induction of apoptosis required bacterial internalization and is associated with intracellular replication. The slow and gradual replication of
S. aureus
inside epithelial cells hints at the role of host factors or signals in bacterial growth and further suggests possible cross talk between host cells and
S. aureus.
Direct Evidence for Involvement of NF-κB in Transcriptional Activation of Tumor Necrosis Factor by a Spirochetal Lipoprotein
Authors: Udalova Irina A. , Vidal Vincent , Scragg Ian G. , Kwiatkowski Dominic 
Published: July 2002

ABSTRACTVariable major lipoprotein (Vmp) is a major tumor necrosis factor (TNF)-inducing component ofBorrelia recurrentis, the agent of louse-borne relapsing fever.B. recurrentisVmp rapidly stimulates nuclear translocation of NF-κB and proinflammatory cytokine gene expression in the human monocyte-like cell line MonoMac 6. By overexpressing disabled mutant IκBα in MonoMac 6 cells cotransfected with a reporter gene, we provide evidence that NF-κB is essential for the transcriptional activation of TNF in this system.
Salmonella
Pathogenicity Island 2 Influences Both Systemic Salmonellosis and
Salmonella
-Induced Enteritis in Calves
Authors: Bispham J. , Tripathi B. N. , Watson P. R. , Wallis T. S. 
Published: July 2002

ABSTRACT

We have used signature-tagged mutagenesis to identify mutants of the host-specific
Salmonella enterica
serotype Dublin which were avirulent in calves and/or BALB/c mice. A mutant with a transposon insertion in the
sseD
gene of
Salmonella
pathogenicity island 2 (SPI-2), which encodes a putative secreted effector protein, was identified. This mutant was recovered from the bovine host but not from the murine host following infection with a pool of serotype Dublin mutants. However, a pure inoculum of the
sseD
mutant was subsequently shown to be attenuated in calves following infection either by the intravenous route or by the oral route. The
sseD
mutant was fully invasive for bovine intestinal mucosa but was subsequently unable to proliferate to the same numbers as the parental strain in vivo. Both the
sseD
mutant and a second SPI-2 mutant, with a transposon insertion in the
ssaT
gene, induced significantly weaker secretory and inflammatory responses in bovine ligated ileal loops than did the parental strain. These results demonstrate that SPI-2 is required by serotype Dublin for the induction of both systemic and enteric salmonellosis in calves.
Enhancement of Innate Immunity againstMycobacterium aviumInfection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase
Authors: Hayashi Tomoko , Rao Savita P. , Takabayashi Kenji , Van Uden John H. , Kornbluth Richard S. , Baird Stephen M. , Taylor Milton W. , Carson Dennis A. , Catanzaro Antonino , Raz Eyal 
Published: July 2002

ABSTRACTBacterial DNA and its synthetic immunostimulatory oligodeoxynucleotide analogs (ISS-ODN) activate innate immunity and promote Th1 and cytotoxic T-lymphocyte immune responses. Based on these activities, we investigated whether ISS-ODN could modify the course ofMycobacterium aviuminfection.M. aviumgrowth in vitro was significantly inhibited by ISS-ODN treatment of human and mouse macrophages, andM. aviumgrowth in vivo was similarly inhibited in C57BL/6 mice treated with ISS-ODN. This protective effect of ISS-ODN was largely independent of tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), nitric oxide, NADPH oxidase, alpha/beta interferon (IFN-α/β), and IFN-γ. In contrast, we found that the induction of indoleamine 2,3-dioxygenase (IDO) was required for the antimycobacterial effect of ISS-ODN. To evaluate the potential for synergism between ISS-ODN and other antimycobacterial agents, treatment with a combination of ISS-ODN and clarithromycin (CLA) was tested in vitro and in vivo. ISS-ODN significantly enhanced the therapeutic effect of CLA in both human and mouse macrophages and in C57BL/6 mice. This study newly identifies IDO as being involved in the antimicrobial activity of ISS-ODN and suggests the usefulness of ISS-ODN when used in combination with conventional chemotherapy for microbial infections.
Phosphorylcholine-Dependent Cross-Reactivity between Dental Plaque Bacteria and Oxidized Low-Density Lipoproteins
Authors: Schenkein Harvey A. , Berry Collin R. , Purkall Donald , Burmeister John A. , Brooks Carol N. , Tew John G. 
Published: July 2002

ABSTRACTAntibodies reactive with phosphorylcholine (PC) are ubiquitous in human sera, but the antigens stimulating their production and their function are not clear. Previous studies have shown that a significant proportion of dental plaque bacteria contain PC as determined by reactivity with PC-specific mouse myeloma proteins and monoclonal antibodies. Additionally, serum antibody concentrations of immunoglobulin (IgG) G anti-PC are higher in sera of individuals who have experienced periodontal attachment loss than those who are periodontally healthy. These data implicate the oral microflora as a source of antigen-stimulating anti-PC responses. Recent data also indicate that antibodies with specificity for PC are elevated in ApoE-deficient mice, a model for studies of athersclerosis, and that such antibodies bound oxidized low-density lipoproteins (LDL) (oxLDL) in atherosclerotic plaques. These data prompted the hypothesis that human anti-PC could bind to both oral bacteria and human oxLDL, and that these antigens are cross-reactive. We therefore examined the ability of human anti-PC to bind to PC-bearing strains of oral bacteria using enzyme-linked immunosorbent inhibition assays and by assessment of direct binding of affinity-purified human anti-PC to PC-bearingActinobacillus actinomycetemcomitans. Our results indicated that PC-bearing strains ofStreptococcus oralis,Streptococcus sanguis,Haemophilus aphrophilus,Actinomyces naeslundii,Fusobacterium nucleatum, andA. actinomycetemcomitans, as well as a strain ofStreptococcus pneumoniae, absorbed up to 80% of anti-PC IgG antibody from human sera. Furthermore, purified anti-PC bound to a PC-bearing strain ofA. actinomycetemcomitansbut only poorly to a PC-negative strain. OxLDL also absorbed anti-PC from human sera, and oxLDL but not LDL reacted with up to 80% of the anti-PC in human sera. Furthermore, purified anti-PC bound directly to oxLDL but not to LDL. The data indicate that PC-containing antigens on a variety of common oral bacteria are cross-reactive with neoantigens expressed in oxLDL. We propose that PC-bearing dental plaque microorganisms may induce an antibody response to PC that could influence the inflammatory response associated with atherosclerosis.
Effects of Alum Adjuvant or a Booster Dose on Immunogenicity during Clinical Trials of Group B Streptococcal Type III Conjugate Vaccines
Authors: Paoletti L. C. , Rench M. A. , Kasper D. L. , Molrine D. , Ambrosino D. , Baker C. J. 
Published: July 2002

ABSTRACT
Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular polysaccharide (CPS)-protein conjugate vaccines in healthy adults have demonstrated their safety and improved immunogenicity compared with uncoupled CPSs. Two recent trials sought to determine (i) whether adsorption of conjugate vaccine to aluminum hydroxide would improve immunogenicity and (ii) whether the CPS-specific immunoglobulin G (IgG) response could be boosted by administration of a second dose. Adsorption of GBS type III CPS-tetanus toxoid (III-TT) conjugate vaccine to alum did not improve the immune response to a 12.5-μg dose in healthy adult recipients. Four weeks after vaccination, the geometric mean antibody concentrations (GMCs) for the 15 recipients of III-TT with or without alum were 3.3 and 3.6 μg/ml, respectively. In the second trial, 36 healthy adults vaccinated previously with GBS III-TT conjugate were given a second 12.5-μg dose 21 months later. At 4 weeks after the second dose, the GMCs of type III CPS-specific IgG were similar to those measured 4 weeks after the primary vaccination, suggesting a lack of a booster response. However, 8 (22%) of the 36 participants who had undetectable III CPS-specific IgG (<0.05 μg/ml) before the first dose of III-TT conjugate exhibited a booster response to the second dose, with a fourfold-greater GMC of type III CPS-specific IgG than after the initial immunization. These results suggest that prior natural exposure to type III GBS or a related antigen may be responsible for the brisk IgG response to CPS noted in most adults after vaccination. However, a second dose of GBS III-TT conjugate vaccine may be required for adults whose initial CPS-specific IgG concentrations are very low and would also restore the initial peak-specific III CPS-IgG in responders to previous vaccination.
Potential Role for a Carbohydrate Moiety in Anti-CandidaActivity of Human Oral Epithelial Cells
Authors: Steele Chad , Leigh Janet , Swoboda Rolf , Ozenci Hatice , Fidel Paul L. 
Published: July 2002

ABSTRACTCandida albicansis both a commensal and a pathogen at the oral mucosa. Although an intricate network of host defense mechanisms are expected for protection against oropharyngeal candidiasis, anti-Candidahost defense mechanisms at the oral mucosa are poorly understood. Our laboratory recently showed that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia and/or hyphal phases of severalCandidaspecies in vitro with a requirement for cell contact and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candidaactivity is resistant to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonoxidative components such as soluble defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti-Candidaactivity was sensitive to heat, paraformaldehyde fixation, and detergents, but these treatments were accompanied by a significant loss in epithelial cell viability. Treatments that removed existing membrane protein or lipid moieties in the presence or absence of protein synthesis inhibitors had no effect on epithelial cell inhibitory activity. In contrast, the epithelial cell-mediated anti-Candidaactivity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence ofC. albicansto oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent studies that evaluated specific membrane carbohydrate moieties, however, showed no role for sulfated polysaccharides, sialic acid residues, or glucose- and mannose-containing carbohydrates. These results suggest that oral epithelial cell-mediated anti-Candidaactivity occurs exclusively with viable epithelial cells through contact withC. albicansby an as-yet-undefined carbohydrate moiety.
Nonimmune Binding of Human Immunoglobulin A (IgA) and IgG Fc by Distinct Sequence Segments of the EibF Cell Surface Protein of
Escherichia coli
Authors: Sandt Carol H. , Hill Charles W. 
Published: July 2002

ABSTRACT

The
eib
genes of
Escherichia coli
encode surface-exposed proteins which bind immunoglobulins (Ig) such as the Fc fragment of human IgG (IgG Fc) in a nonimmune manner. The Eib proteins belong to a family which includes YadA of
Yersinia
, UspA2 of
Moraxella
, and DsrA of
Haemophilus ducreyi.
This family of surface-exposed proteins shares several features, such as the ability to impart resistance to human serum complement and a tendency to exist as stable multimers. Four genes,
eibA
,
eibC
,
eibD
and
eibE
, were previously identified and cloned from ECOR-9, a strain from the
E. coli
reference collection. EibC, -D, and -E bind human serum IgA in addition to IgG, but no IgA binding has been observed for EibA. Here, we report the cloning of a new
eib
gene,
eibF
, from a second strain of
E. coli
, ECOR-2. The product, EibF, has a relatively strong preference for IgA. Like the other
eib
genes,
eibF
attenuates serum sensitivity, occurs as a stable multimer, and is associated with a prophage. By subcloning portions of the
eibA
and
eibF
genes, we have identified distinct sequence segments sufficient to cause Ig binding, multimerization, and discrimination between IgA and IgG. The ability to multimerize is associated with a sequence close to the C terminus that is homologous to other family members such as YadA. Binding of IgG Fc is associated with a sequence that is highly conserved among all Eib proteins but otherwise unique. Binding of IgA is associated with a sequence of EibF that is not similar to any EibA sequence.
Role of the Classical Pathway of Complement Activation in Experimentally Induced Polymicrobial Peritonitis
Authors: Celik Ilhan , Stover Cordula , Botto Marina , Thiel Steffen , Tzima Sotiria , Künkel Dieter , Walport Mark , Lorenz Wilfried , Schwaeble Wilhelm 
Published: July 2002

ABSTRACTThe complement system and the natural antibody repertoire provide a critical first-line defense against infection. The binding of natural antibodies to microbial surfaces opsonizes invading microorganisms and activates complement via the classical pathway. Both defense systems cooperate within the innate immune response. We studied the role of the complement system in the host defense against experimental polymicrobial peritonitis using mice lacking either C1q or factor B and C2. The C1q-deficient mice lacked the classical pathway of complement activation. The factor B- and C2-deficient mice were known to lack the classical and alternative pathways, and we demonstrate here that these mice also lacked the lectin pathway of complement activation. Using inoculum doses adjusted to cause 42% mortality in the wild-type strain, none of the mice deficient in the three activation routes of complement (factor B and C2 deficient) survived (mortality of 100%). Mortality in mice deficient only in the classical pathway of complement activation (C1q deficient) was 83%. Application of further dilutions of the polymicrobial inoculum showed a dose-dependent decrease of mortality in wild-type controls, whereas no changes in mortality were observed in the two gene-targeted strains. These results demonstrate that the classical activation pathway is required for an effective antimicrobial immune defense in polymicrobial peritonitis and that, in the infection model used, the remaining antibody-independent complement activation routes (alternative and lectin pathways) provide a supporting line of defense to gain residual protection in classical pathway deficiency.
Role of Gamma Interferon in the Pathogenesis of Severe Schistosomiasis in Interleukin-4-Deficient Mice
Authors: La Flamme Anne Camille , Patton Elisabeth A. , Pearce Edward J. 
Published: July 2002

ABSTRACTIn the absence of interleukin-4 (IL-4), infection withSchistosoma mansonileads to a severe fatal disease rather than the chronic survivable condition that occurs in wild-type (WT) mice. Because the sustained production of NO most closely correlates to weight loss and fatality in infected IL-4−/−mice and because gamma interferon (IFN-γ) is an important inducer of inducible NO synthase, infected IL-4−/−mice were treated with anti-IFN-γ antibodies to determine the role of IFN-γ during schistosomiasis in WT and IL-4−/−animals. When IFN-γ was neutralized, Th2 responses were enhanced and NO production was reduced in both WT and IL-4−/−mice. The decreased NO production correlated with a rescue of proliferation in splenocytes from infected IL-4−/−mice. Furthermore, the neutralization of IFN-γ in vivo improved the gross appearance of the liver and led to a reduction in granuloma size in infected IL-4−/−but not WT mice. However, the neutralization of IFN-γ in vivo did not affect the development of severe disease in infected IL-4−/−mice. These results suggest that while the increased production of IFN-γ does lead to some of the pathology observed in infected IL-4−/−mice, it is not ultimately responsible for cachexia and death.
The Inducible Nitric Oxide Synthase Locus Confers Protection against Aerogenic Challenge of Both Clinical and Laboratory Strains ofMycobacterium tuberculosisin Mice
Authors: Scanga Charles A. , Mohan Vellore P. , Tanaka Kathryn , Alland David , Flynn JoAnne L. , Chan John 
Published: July 2002

ABSTRACTMurine macrophages effect potent antimycobacterial function via the production of nitric oxide by the inducible isoform of the enzyme nitric oxide synthase (NOS2). The protective role of reactive nitrogen intermediates (RNI) againstMycobacterium tuberculosisinfection has been well established in various murine experimental tuberculosis models using laboratory strains of the tubercle bacillus to establish infection by the intravenous route. However, important questions remain about the in vivo importance of RNI in host defense againstM. tuberculosis. There is some evidence that RNI play a lesser role following aerogenic, rather than intravenous,M. tuberculosisinfection of mice. Furthermore, in vitro studies have demonstrated that different strains ofM. tuberculosis, including clinical isolates, vary widely in their susceptibility to the antimycobacterial effects of RNI. Thus, we sought to test rigorously the protective role of RNI against infection with recent clinical isolates ofM. tuberculosisfollowing both aerogenic and intravenous challenges. Three recently isolated and uniqueM. tuberculosisstrains were used to infect both wild-type (wt) C57BL/6 andNOS2gene-disrupted mice. Regardless of the route of infection, NOS2−/−mice were much more susceptible than wt mice to any of the clinical isolates or to either the Erdman or H37Rv laboratory strain ofM. tuberculosis. Mycobacteria replicated to much higher levels in the organs of NOS2−/−mice than in those of wt mice. Although the clinical isolates all exhibited enhanced virulence in NOS2−/−mice, they displayed distinct growth rates in vivo. The present study has provided results indicating that RNI are required for the control of murine tuberculous infection caused by both laboratory and clinical strains ofM. tuberculosis. This protective role of RNI is essential for the control of infection established by either intravenous or aerogenic challenge.
Temporal and Spatial Arrangement of Lymphocytes within Lung Granulomas Induced by Aerosol Infection withMycobacterium tuberculosis
Authors: Gonzalez-Juarrero Mercedes , Turner Oliver C. , Turner Joanne , Marietta Peter , Brooks Jason V. , Orme Ian M. 
Published: July 2002

ABSTRACTThe progression of the immune response in the lungs after aerosol infection withMycobacterium tuberculosisis a complex cellular event dominated by macrophages and lymphocytes. Although the phenotype of lymphocytes participating in this response is becoming increasingly well characterized, the dynamic influx of these cells during the infection and their spatial arrangements within the lung tissue are still poorly understood. This study shows that in the first month after aerosol infection withM. tuberculosisthere was a steady increase in the percentages of total CD3+, CD3+CD4+and CD3+CD8+cells, with consistently larger numbers of CD3+CD4+cells than of CD3+CD8+cells. As granuloma formation continued, the granuloma was found to consist of macrophages, CD4, and CD8 T cells, as well as a smaller number of B cells. Whereas CD4 T cells formed organized aggregates, CD8 T cells were fewer and more scattered and tended to be more prominent toward the periphery of the granulomas. The possible ramifications of the juxtapositions of these two major T-cell subsets are discussed.
Expression of Hemin Receptor Molecule ChuA Is Influenced by RfaH in Uropathogenic
Escherichia coli
Strain 536
Authors: Nagy Gábor , Dobrindt Ulrich , Kupfer Maren , Emödy Levente , Karch Helge , Hacker Jörg 
Published: July 2002

ABSTRACT

The outer membrane protein ChuA responsible for hemin utilization has been recently identified in several pathogenic
Escherichia coli
strains. We report that the regulatory protein RfaH influences ChuA expression in the uropathogenic
E. coli
strain 536. In an
rfaH
mutant, the
chuA
transcript as well as the ChuA protein levels were significantly decreased in comparison with those in the wild-type strain. Within the
chuA
gene, a consensus motif known as the JUMPStart (just upstream of many polysaccharide associated gene starts) sequence was found, which is shared by RfaH-affected operons. Furthermore, the presence of two different subclasses of the
chuA
determinant and their distribution in
E. coli
pathogroups are described.
Legionella pneumophilaSuppresses Interleukin-12 Production by Macrophages
Authors: Matsunaga Kazuto , Klein Thomas W. , Newton Catherine , Friedman Herman , Yamamoto Yoshimasa 
Published: July 2002

ABSTRACTIn vitro infection of macrophages withLegionella pneumophilainduced interleukin-1α (IL-1α), IL-10, monocyte chemotactic protein 1 (MCP-1), and MCP-3 but not IL-12. The lipopolysaccharide (LPS)-induced production of IL-12 was down-regulated by infection with virulentL. pneumophila, but other cytokines were not affected. In contrast, avirulentL. pneumophilaor UV-killed, virulentL. pneumophiladid not induce any suppression of IL-12. The IL-12 suppression occurred at the level of mRNA accumulation for IL-12 genes in response to LPS stimulation, but the infection induced a marked accumulation of mRNA for both MCP-1 and MCP-3, which are known to suppress IL-12 production in LPS-stimulated macrophages. However, pretreatment of macrophages with MCP-1 did not suppress LPS-induced IL-12 production at the concentrations induced byL. pneumophilainfection. These results suggest thatL. pneumophilaselectively suppresses IL-12 production induced by LPS from macrophages in vitro by an MCP-independent mechanism.