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Berlin Brandenburg

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  • 1
    Language: English
    In: The Journal of infectious diseases, 15 April 2008, Vol.197(8), pp.1103-9
    Description: Haemophilus ducreyi contains 3 TonB-dependent receptors: the hemoglobin receptor HgbA, which is required for virulence in humans; the heme receptor TdhA; and an uncharacterized conserved hypothetical protein TdX (HD0646). A double tdX/tdhA mutant (FX527) was constructed on the background of a human-passaged variant of strain 35000 (35000HP). Six volunteers were infected with 35000HP at 3 sites on one arm and with FX527 at 3 sites on the other. The pustule formation rate was 55.6% (95% confidence interval [CI], 35.7%-75.4%) at 18 parent-strain sites and 44.4% (95% CI, 15.0%-73.9%) at 18 mutant-strain sites (P = .51). Similar amounts of 35000HP and FX527 were recovered from pustules in semiquantitative culture. Thus, TdX and TdhA are not necessary for virulence, whereas HgbA is both necessary and sufficient for virulence in humans. The data suggest that hemoglobin is the sole source of heme/iron used by H. ducreyi in vivo and has implications for the potential of HgbA as a vaccine.
    Keywords: Bacterial Outer Membrane Proteins -- Biosynthesis ; Bacterial Proteins -- Biosynthesis ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Pathogenicity ; Membrane Proteins -- Biosynthesis
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 2
    Language: English
    In: The Journal of infectious diseases, 01 June 2008, Vol.197(11), pp.1531-6
    Description: Haemophilus ducreyi 35000HP contains a cluster of homologues of genes required for the synthesis of enterobacterial common antigen (ECA), suggesting that H. ducreyi may express a putative ECA-like glycoconjugate. WecA initiates the synthesis of ECA by transferring N-acetylglucosamine to undecaprenyl-P, to form lipid I. A wecA mutant (35000HPwecA) was constructed, and 5 volunteers were inoculated at 3 sites with fixed doses of 35000HP on one arm and at 3 sites with varying doses of 35000HPwecA on the other arm. 35000HPwecA caused pustules to form at 3 sites inoculated with a dose 2.5-fold higher than that of 35000HP. However, at sites inoculated with similar doses of 35000HP and 35000HPwecA, pustules developed at 46.7% (95% confidence interval [CI], 23.3%-70.0%) of 15 parent-strain sites and at 8.3% (95% CI, 0.01%-23.6%) of 12 mutant-strain sites (P = .013). Thus, the expression of wecA contributes to the ability of H. ducreyi to cause pustules in humans.
    Keywords: Multigene Family ; Antigens, Bacterial -- Genetics ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Genetics
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 3
    Language: English
    In: The Journal of infectious diseases, 15 May 2007, Vol.195(10), pp.1443-51
    Description: We infected 11 HIV-seropositive volunteers whose CD4(+) cell counts were 〉350 cells/ microL (7 of whom were receiving antiretrovirals) with Haemophilus ducreyi. The papule and pustule formation rates were similar to those observed in HIV-seronegative historical control subjects. No subject experienced a sustained change in CD4(+) cell count or HIV RNA level. The cellular infiltrate in biopsy samples obtained from the HIV-seropositive and HIV-seronegative subjects did not differ with respect to the percentage of leukocytes, neutrophils, macrophages, or T cells. The CD4(+):CD8(+) cell ratio in biopsy samples from the HIV-seropositive subjects was 1:3, the inverse of the ratio seen in the HIV-seronegative subjects (P〈.0001). Although CD4(+) cells proliferated in lesions, in situ hybridization and reverse-transcription polymerase chain reaction for HIV RNA was negative. We conclude that experimental infection in HIV-seropositive persons is clinically similar to infection in HIV-seronegative persons and does not cause local or augment systemic viral replication. Thus, prompt treatment of chancroid may abrogate increases in viral replication associated with natural disease.
    Keywords: Chancroid -- Complications ; HIV Infections -- Complications ; Haemophilus Ducreyi -- Physiology
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 4
    Language: English
    In: The Journal of Infectious Diseases, 1 March 2000, Vol.181(3), pp.1049-1054
    Description: Haemophilus ducreyi expresses a conserved hemoglobin-binding outer-membrane protein (HgbA). To test the role of HgbA in pathogenesis, we infected 9 adults with isolate 35000 and its isogenic hgbA-inactivated mutant (FX504) on their upper arms in a double-blinded, escalating dose-response study. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule-formation rate was 55% (95% confidence interval [CI], 30.8%-78.5%) at parent sites and 0 (95% CI, 0-10.5%) at mutant sites (P 〈 .0001). The recovery rate of H. ducreyi from surface cultures was 16% (n = 142) from parent sites and 0 (n = 213) from mutant sites (P 〈 .0001). H. ducreyi was recovered at biopsy from 6 of 7 parent sites and from 0 of 3 mutant sites. The results indicate that hemoglobin may be a critical source of heme or iron for the establishment of H. ducreyi infection in humans.
    Keywords: Physical sciences -- Chemistry -- Chemical compounds -- Haemophilus ducreyi ; Biological sciences -- Biology -- Microbiology -- Haemophilus ducreyi ; Biological sciences -- Biology -- Microbiology -- Haemophilus ducreyi ; Health sciences -- Medical conditions -- Infections -- Haemophilus ducreyi ; Physical sciences -- Chemistry -- Chemical compounds -- Haemophilus ducreyi ; Health sciences -- Medical diagnosis -- Diagnostic methods -- Haemophilus ducreyi ; Health sciences -- Medical sciences -- Pharmacology -- Haemophilus ducreyi ; Health sciences -- Medical sciences -- Immunology -- Haemophilus ducreyi ; Health sciences -- Medical conditions -- Physical trauma -- Haemophilus ducreyi ; Health sciences -- Health and wellness -- Public health -- Haemophilus ducreyi
    ISSN: 00221899
    E-ISSN: 15376613
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  • 5
    Language: English
    In: The Journal of Infectious Diseases, 1 June 1998, Vol.177(6), pp.1608-1613
    Description: Human subjects were infected with Haemophilus ducreyi. All subjects developed papules and were randomized to treatment with a single dose of azithromycin (1 g) or ciprofloxacin (500 mg). At weekly intervals, volunteers were reinoculated with H. ducreyi, and drug concentrations were measured in peripheral blood mononuclear cells (PBMC). When papules developed, the subjects were treated with antibiotics and dismissed from the study. Eight of the ciprofloxacin-treated subjects developed papules 1 week after the initial treatment, and the ninth subject developed disease 2 weeks after treatment. The 9 azithromycin-treated subjects developed papules 4-10 weeks (mean, 6.8) after the initial treatment (P 〈 .001). Azithromycin was detected in PBMC for 3-6 weeks (mean, 4). Pre-and posttreatment lesions had histology typical of experimental chancroid or were culture positive. Azithromycin prevents experimental chancroid for nearly 2 months. These findings have implications for strategies to prevent chancroid.
    Keywords: Health sciences -- Medical conditions -- Infections -- Haemophilus ducreyi ; Health sciences -- Medical sciences -- Pharmacology -- HIV ; Health sciences -- Medical conditions -- Infections -- HIV ; Health sciences -- Medical diagnosis -- Diagnostic methods -- HIV ; Biological sciences -- Biology -- Microbiology -- HIV ; Biological sciences -- Biology -- Microbiology -- HIV ; Biological sciences -- Biology -- Microbiology -- HIV ; Health sciences -- Medical specialties -- Pathology -- HIV ; Health sciences -- Medical conditions -- Physical trauma -- HIV ; Physical sciences -- Physics -- Microphysics -- HIV
    ISSN: 00221899
    E-ISSN: 15376613
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  • 6
    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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  • 7
    Language: English
    In: The Journal of Infectious Diseases, 1 March 2000, Vol.181(3), pp.1176-1179
    Description: Haemophilus ducreyi expresses fine tangled pili, which are composed predominantly of a major subunit (FtpA). Confocal microscopy showed that an FtpA-specific monoclonal antibody bound to bacteria in biopsy samples obtained from infected human volunteers. To test the role of pili in pathogenesis, an isogenic mutant (35000HP-SMS1) was constructed by insertionally inactivating ftpA 35000HP-SMS1 did not express FtpA and was nonpiliated but was otherwise identical to its parent, 35000HP. Seven healthy adults were challenged on the upper arm with the isogenic isolates in a double-blinded, escalating dose-response study. Sites inoculated with the mutant produced papules and pustules at rates similar to the rates observed at sites inoculated with the parent. The recovery rate of H. ducreyi from cultures and the histopathology of biopsy samples obtained from pustules inoculated with 35000HP or 35000HP-SMS1 were similar. Although pili are expressed in vivo, FtpA is not required for pustule formation in the human challenge model.
    Keywords: Biological sciences -- Biology -- Microbiology -- Haemophilus ducreyi ; Health sciences -- Medical diagnosis -- Diagnostic methods -- Polyclonal antibodies ; Biological sciences -- Biology -- Microbiology -- Polyclonal antibodies ; Health sciences -- Medical conditions -- Physical trauma -- Polyclonal antibodies ; Health sciences -- Medical conditions -- Infections -- Polyclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Polyclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Polyclonal antibodies ; Applied sciences -- Laboratory techniques -- Microscopy -- Polyclonal antibodies ; Health sciences -- Medical sciences -- Immunology -- Polyclonal antibodies ; Physical sciences -- Chemistry -- Chemical compounds -- Polyclonal antibodies
    ISSN: 00221899
    E-ISSN: 15376613
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