Inactivation of the Haemophilus ducreyi luxS Gene Affects the Virulence of this Pathogen in Human Subjects

Abstract

Haemophilus ducreyi 35000HP contains a homolog of the luxS gene, which encodes an enzyme that synthesizes the AI-2 autoinducer in other gram-negative bacteria. H. ducreyi 35000HP produced AI-2 that functioned in a Vibrio harveyi-based reporter system. An H. ducreyi luxS mutant was constructed by insertional inactivation of the luxS gene and lost the ability to produce AI-2. Provision of the H. ducreyi luxS gene in trans partially restored AI-2 production by the mutant. The luxS mutant was compared to its parent for virulence in the human challenge model of experimental chancroid. The pustule formation rate in five volunteers was 93.3% (95% CI, 81.7, 99.9) at 15 parent sites and 60.0% (95% CI, 48.3, 71.7) at 15 mutant sites (one-tailed P = 0.0002). Thus, the luxS mutant was partially attenuated for virulence. This is the first report of AI-2 production contributing to the pathogenesis of a genital ulcer disease.