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

Labandeira-Rey, Maria; Janowicz, Diane M.; Blick, Robert J.; Fortney, Kate R.; Zwickl, Beth; Katz, Barry P.; Spinola, Stanley M.; Hansen, Eric J.
August 2009
Journal of Infectious Diseases;8/1/2009, Vol. 200 Issue 3, p409
Academic Journal
Haemophilus ducreyi 35000HP contains a homologue of the luxS gene, which encodes an enzyme that synthesizes autoinducer 2 (AI-2) in other gram-negative bacteria. H. ducreyi 35000HP produced AI-2 that functioned in a Vibrio harveyi-based reporter system. A 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 with its parent for virulence in the human challenge model of experimental chancroid. The pustule-formation rate in 5 volunteers was 93.3% (95% confidence interval, 81.7%-99.9%) at 15 parent sites and 60.0% (95% confidence interval, 48.3%-71.7%) at 15 mutant sites (1-tailed P < .001). 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.


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