4.7 Article Proceedings Paper

A Fibrinogen-Binding Lipoprotein Contributes to the Virulence of Haemophilus ducreyi in Humans

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 199, Issue 5, Pages 684-692

Publisher

UNIV CHICAGO PRESS
DOI: 10.1086/596656

Keywords

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Funding

  1. NCRR NIH HHS [M01 RR00750, M01 RR000750, M01 RR000750-36] Funding Source: Medline
  2. NIAID NIH HHS [K08 AI074657, R01 AI027863-16, R01 AI27863, T32 AI07637, U19 AI031494, K08 AI074657-01, T32 AI007637, U19 AI31494, T32 AI007637-07, U19 AI031494-17, K08 AI74657, R01 AI027863] Funding Source: Medline

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A gene expression study of Haemophilus ducreyi identified the hypothetical lipoprotein HD0192, renamed here fibrinogen binder A(FgbA), as being preferentially expressed in vivo. To test the role played by fgbA in virulence, an isogenic fgbA mutant (35000HPfgbA) was constructed using H. ducreyi 35000HP, and 6 volunteers were experimentally infected with 35000HP or 35000HPfgbA. The overall pustule-formation rate was 61.1% at parent sites and 22.2% at mutant sites (P = .019). Papules were significantly smaller at mutant sites than at parent sites (13.3 vs. 37.9 mm(2); P = .002) 24 h after inoculation. Thus, fgbA contributed significantly to the virulence of H. ducreyi in humans. In vitro experiments demonstrated that fgbA encodes a fibrinogen-binding protein; no other fibrinogen-binding proteins were identified in 35000HP. fgbA was conserved among clinical isolates of both class I and II H. ducreyi strains, supporting the finding that fgbA is important for H. ducreyi infection.

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