Haemophilus ducreyi is the causative agent of chancroid, a sexually transmitted genital ulcerative disease. Chancroid is common in the developing world and occurs sporadically in North American. In addition to the rabidity due to chancroid, genital ulcers are thought to facilitate the heterosexual transmission of the HIV virus. The molecular mechanism(s) responsible for formation of the chancroid ulcer are not known. We have identified a toxin which has hemolytic activity directed against horse erythrocytes. We hypothesize that this hemolysin has cytotoxic activity directed against human cells and plays a direct role in the formation of the chancroid ulcer. We will employe genetic an biochemical approaches to characterize this toxin. The structural gene(s) will be cloned, sequenced and expressed in E> coli. Mutants of H. ducreyi deficient in production of the toxin will be constructed by allele replacement and tested for virulence in in vitro models, a rabbit model, and in human challenge studies. These studies will broaden our outstanding of the hemolysin by providing data on in vivo targets of this activity, and by providing data on the role of the hemolysin in the pathogenesis of the human chancroid lesion.
