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

Abstract

A gene expression study of Haemophilus ducreyi identified the hypothetical lipoprotein HD0192, renamed here fibrinogen binder A (fgbA), as preferentially expressed in vivo. To test the role of fgbA in virulence, an isogenic fgbA mutant (35000HPfgbA) was constructed in H. ducreyi 35000HP, and six volunteers were experimentally infected with 35000HP and 35000HPfgbA. The overall pustule formation rate was 61.1% at parent sites and 22.2% at mutant sites (P = 0.019). Papules were significantly smaller at mutant sites than at parent sites (13.3 versus 37.9 mm2, P = 0.002) 24 h after inoculation. Thus, fgbA contributed significantly to virulence of H. ducreyi in humans. In vitro studies 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 class II H. ducreyi strains, supporting the finding that fgbA is important for H. ducreyi infection.