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  • Oxford University Press (CrossRef)  (8)
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  • 1
    Language: English
    In: The Journal of infectious diseases, 15 June 2011, Vol.203(12), pp.1859-65
    Description: Haemophilus ducreyi 35000HP contains a homolog of the CpxRA 2-component signal transduction system, which controls the cell envelope stress response system in other gram-negative bacteria and regulates some important H. ducreyi virulence factors. A H. ducreyi cpxR mutant was compared with its parent for virulence in the human challenge model of experimental chancroid. The pustule formation rate in 5 volunteers was 33% (95% confidence interval [CI], 1.3%-65.3%) at 15 parent sites and 40% (95% CI, 18.1%-61.9%) at 15 mutant sites (P = .35). Thus, the cpxR mutant was not attenuated for virulence. Inactivation of the H. ducreyi cpxR gene did not reduce the ability of this mutant to express certain proven virulence factors, including the DsrA serum resistance protein and the LspA2 protein, which inhibits phagocytosis. These results expand our understanding of the involvement of the CpxRA system in regulating virulence expression in H. ducreyi.
    Keywords: Bacterial Proteins -- Genetics ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Genetics
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 2
    Language: English
    In: The Journal of infectious diseases, November 2012, Vol.206(9), pp.1407-14
    Description: Haemophilus ducreyi encounters several classes of antimicrobial peptides (APs) in vivo and utilizes the sensitive-to-antimicrobial-peptides (Sap) transporter as one mechanism of AP resistance. A mutant lacking the periplasmic solute-binding component, SapA, was somewhat more sensitive to the cathelicidin LL-37 than the parent strain and was partially attenuated for virulence. The partial attenuation led us to question whether the transporter is fully abrogated in the sapA mutant. We generated a nonpolar sapBC mutant, which lacks both inner membrane permeases of the Sap transporter, and tested the mutant for virulence in human volunteers. In vitro, we compared LL-37 resistance phenotypes of the sapBC and sapA mutants. Unlike the sapA mutant, the sapBC mutant was fully attenuated for virulence in human volunteers. In vitro, the sapBC mutant exhibited significantly greater sensitivity than the sapA mutant to killing by LL-37. Similar to the sapA mutant, the sapBC mutant did not affect H. ducreyi's resistance to human defensins. Compared with the sapA mutant, the sapBC mutant exhibited greater attenuation in vivo, which directly correlated with increased sensitivity to LL-37 in vitro. These results strongly suggest that the SapBC channel retains activity when SapA is removed.
    Keywords: Drug Resistance, Bacterial ; Antimicrobial Cationic Peptides -- Pharmacology ; Haemophilus Ducreyi -- Enzymology ; Membrane Transport Proteins -- Metabolism ; Virulence Factors -- Metabolism
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 3
    In: The Journal of Infectious Diseases, 2016, Vol. 214(3), pp.489-495
    Description: Background.  In humans inoculated with Haemophilus ducreyi , there are host effects on the possible clinical outcomes—pustule formation versus spontaneous resolution of infection. However, the immunogenetic factors that influence these outcomes are unknown. Here we examined the role of 14 single-nucleotide polymorphisms (SNPs) in 7 selected pathogen-recognition pathways and cytokine genes on the gradated outcomes of experimental infection. Methods.  DNAs from 105 volunteers infected with H. ducreyi at 3 sites were genotyped for SNPs, using real-time polymerase chain reaction. The participants were classified into 2 cohorts, by race, and into 4 groups, based on whether they formed 0, 1, 2, or 3 pustules. χ 2 tests for trend and logistic regression analyses were performed on the data. Results.  In European Americans, the most significant findings were a protective association of the TLR9 +2848 GG genotype and a risk-enhancing association of the TLR9 TA haplotype with pustule formation; logistic regression showed a trend toward protection for the TLR9 +2848 GG genotype. In African Americans, logistic regression showed a protective effect for the IL10 – 2849 AA genotype and a risk-enhancing effect for the IL10 AAC haplotype. Conclusions.  Variations in TLR9 and IL10 are associated with the outcome of H. ducreyi infection.
    Keywords: 〈Kwd〉〈Italic Toggle="Yes"〉Haemophilus Ducreyi〈/Italic〉〈/Kwd〉 ; Chancroid ; Skin Ulcers ; Immunogenetics ; Humans ; Innate Immunity
    ISSN: 0022-1899
    E-ISSN: 1537-6613
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  • 4
    In: Clinical Infectious Diseases, 2018, Vol. 67(11), pp.1768-1774
    Description: Haemophilus ducreyi is a major cause of skin ulcers in the tropics. On an endemic island, multiple strains of H. ducreyi cause infection, coinfections are common, and mass treatment with azithromycin did not exert selection pressure on the organism.
    Keywords: 〈Kwd〉 〈Italic Toggle="Yes"〉Haemophilus Ducreyi〈/Italic〉 〈/Kwd〉 ; Cutaneous Ulcers ; Single - Locus Typing ; Molecular Epidemiology
    ISSN: 1058-4838
    E-ISSN: 1537-6591
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  • 5
    Language: English
    In: The Journal of Infectious Diseases, 1 February 1990, Vol.161(2), pp.336-339
    Description: The development of vaccines to prevent Neisseria infections has been impeded by antigenic diversity of most Neisseria surface components. The lipid-modified azurin (Laz), one of two distinct surface proteins recognized by the H.8 monoclonal antibody, is present in all pathogenic Neisseria. The mature protein has two domains; one contains an H.8 epitope and the other has extensive homology to azurins, a class of bacterial copper-binding proteins. The cellular location of Laz and the serum immune response to Laz were examined in patients with disseminated Neisseria infections. The data demonstrated that Laz is probably contained in the Neisseria outer membrane, although unlike most outer membrane proteins it is Sarkosyl soluble. By probing recombinant bacteriophages encoding the H.8 and azurin domains of Laz, results showed that whereas the H.8 epitope is immunogenic in patients with disseminated Neisseria infections, the azurin domain of Laz plays little role in eliciting an antibody response in these patients.
    Keywords: Biological sciences -- Biology -- Microbiology -- Epitopes ; Physical sciences -- Chemistry -- Chemical compounds -- Polyclonal antibodies ; Health sciences -- Medical conditions -- Infections -- Monoclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Monoclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Monoclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Monoclonal antibodies ; Physical sciences -- Astronomy -- Astronomical cosmology -- Monoclonal antibodies ; Physical sciences -- Chemistry -- Chemical compounds -- Monoclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Monoclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Monoclonal antibodies
    ISSN: 00221899
    E-ISSN: 15376613
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  • 6
    Language: English
    In: The Journal of Infectious Diseases, 1 July 1986, Vol.154(1), pp.100-109
    Description: Eighty-six nasopharyngeal isolates of Haemophilus influenzae were prospectively obtained from three children who attended a day care center from infancy until early childhood (five to seven years). A majority of the strains were nontypable. We analyzed strains by comparing their biotypes and by performing electrophoresis of outer membrane proteins on polyacrylamide gels. Profiles of outer membrane proteins were very heterogeneous and could not be used as the basis for the development of a subtyping scheme. The children characteristically carried a nasopharyngeal strain defined by a unique outer membrane pattern for a period of months, lost it, and then acquired a new strain. We probed the outer membrane proteins of a child's strains by the western blot technique with serum obtained serially from the child. Isolates whose outer membrane proteins appeared identical on stained gels generally had similar antigenic bands on western blots but were occasionally immunologically distinct. Serum immunoglobulins of the IgG class that reacted with the outer membrane proteins did not appear to change greatly over time or to play a role in preventing or terminating colonization. We conclude that nasopharyngeal colonization in children by nontypable H. influenzae is a dynamic process and that factors that cause loss and acquisition of strains remain to be determined
    Keywords: Biological sciences -- Biology -- Microbiology ; Health sciences -- Medical sciences -- Immunology ; Applied sciences -- Materials science -- Materials ; Health sciences -- Medical sciences -- Immunology ; Behavioral sciences -- Sociology -- Human societies ; Health sciences -- Medical conditions -- Infections ; Health sciences -- Health and wellness -- Public health ; Health sciences -- Medical conditions -- Infections ; Physical sciences -- Chemistry -- Chemical compounds ; Health sciences -- Medical conditions -- Diseases
    ISSN: 00221899
    E-ISSN: 15376613
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  • 7
    Language: English
    In: The Journal of Infectious Diseases, 1 May 1994, Vol.169(5), pp.1146-1150
    Description: Four subjects were experimentally infected with Haemophilus ducreyi. Lesions developed only at sites where live bacteria were inoculated on abraded skin. No subject developed fever, lymphadenopathy, or disseminated infection during a 3-day observation period. Two subjects who were rechallenged 2 months after initial infection also developed lesions. The amount of H. ducreyi recovered from 10 of 12 biopsies that were semiquantitatively cultured varied widely. Similar histologic features were present in initial and second infections. The epidermis contained pustules; the dermis contained an infiltrate of T cells and macrophages and reactive endothelial cells. Keratinocytes and T cells expressed HLA-DR, consistent with a delayed-type hypersensitivity response. The subjects did not mount humoral responses to bacterial proteins and to lipooligosaccharides after primary and secondary challenges. Thus, human experimental infection with H. ducreyi is well tolerated and safe. Recruitment of T cells and macrophages into chancroid lesions may partially explain the association between chancroid and human immunodeficiency virus transmission.
    Keywords: Biological sciences -- Biology -- Physiology -- Heterophils ; Biological sciences -- Biology -- Physiology -- Heterophils ; Health sciences -- Medical conditions -- Infections -- Heterophils ; Biological sciences -- Biology -- Physiology -- Heterophils ; Biological sciences -- Biochemistry -- Biomolecules -- Heterophils ; Biological sciences -- Biochemistry -- Biomolecules -- Heterophils ; Health sciences -- Medical conditions -- Diseases -- Heterophils ; Health sciences -- Medical conditions -- Infections -- Heterophils ; Biological sciences -- Biochemistry -- Biomolecules -- Heterophils ; Health sciences -- Medical conditions -- Diseases -- Heterophils
    ISSN: 00221899
    E-ISSN: 15376613
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  • 8
    Language: English
    In: The Journal of Infectious Diseases, 1 February 1996, Vol.173(2), pp.394-402
    Description: Human subjects were experimentally infected with Haemophilus ducreyi for up to 2 weeks. Bacterial suspensions were delivered into the epidermis and dermis through puncture wounds made by an allergy-testing device. Subjects developed papular lesions that evolved into pustules resembling natural disease. Some papular lesions resolved spontaneously, indicating that host responses may clear infection. Bacteria were shed intermittently from lesions, suggesting that H. ducreyi may be transmissible before ulceration. Host responses to infection consisted primarily of cutaneous infiltrate of polymorphonuclear leukocytes, Langerhans cells, macrophages, and CD4 T cells of α/β lineage. Expression of HLA-DR by keratinocytes was associated with the presence of interferon-γ mRNA in the skin. There was little evidence for humoral or peripheral blood mononuclear cell responses to bacterial antigens. The cutaneous infiltrate of CD4 cells and macrophages provides a mechanism that facilitates transmission of human immunodeficiency virus by H. ducreyi.
    Keywords: Health sciences -- Medical conditions -- Physical trauma -- Lymphocytes ; Biological sciences -- Biology -- Anatomy -- Lymphocytes ; Health sciences -- Medical sciences -- Immunology -- Lymphocytes ; Health sciences -- Medical conditions -- Infections -- Lymphocytes ; Biological sciences -- Biology -- Physiology -- Lymphocytes ; Biological sciences -- Biology -- Microbiology -- Lymphocytes ; Health sciences -- Medical conditions -- Infections -- Lymphocytes ; Health sciences -- Medical sciences -- Immunology -- Lymphocytes ; Health sciences -- Medical diagnosis -- Diagnostic methods -- Lymphocytes ; Health sciences -- Medical sciences -- Pharmacology -- Lymphocytes
    ISSN: 00221899
    E-ISSN: 15376613
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