Expression of Peptidoglycan-Associated Lipoprotein Is Required for Virulence in the Human Model ofHaemophilus ducreyiInfection

• DOI: 10.1128/iai.68.11.6441-6448.2000
• Publication Date: 2002-07-27T09:58:18Z
• Authors: Kate R. Fortney; Royden S. Young; Margaret E. Bauer; Barry P. Katz; Antoinette F. Hood; Robert S. Munson; Stanley M. Spinola
• Keywords: Haemophilus ducreyi

Haemophilus ducreyi expresses a peptidoglycan-associated lipoprotein (PAL) that exhibits extensive homology to influenzae protein 6. We constructed an isogenic PAL mutant (35000HP-SMS4) by the use of suicide vector contains lacZ as counterselectable marker. H. 35000HP-SMS4 and its parent, 35000HP, had similar growth rates in broth lipooligosaccharide profiles. formed smaller, more transparent colonies than 35000HP and, unlike was hypersensitive antibiotics. Complementation trans restored parental phenotypes. To test whether expression is required for virulence, nine human volunteers were experimentally infected. Each subject inoculated with two doses (41 89 CFU) live one dose heat-killed bacteria on arm three (ranging from 28 800 other arm. Papules developed at sites or parent but significantly smaller mutant-inoculated parent-inoculated sites. The pustule formation rate 72% (95% confidence interval [CI], 46.5 90.3%) 18 11% CI, 2.4 29.2%) 27 (P < 0.0001). recovery surface cultures 8% (n = 130; 95% 4.3 14.6%) 0% 120; 0.0 2.5%) 0.001). recovered six seven biopsied Confocal microscopy confirmed present inoculation site lacked PAL-specific epitope. Although biosafety regulations precluded our testing complemented humans, these results suggest facilitates ability progress pustular stage disease.