Haemophilus ducreyi causes a sexually transmitted genital ulcer disease, chancroid, implicated in increased heterosexual transmission of HIV. The genetic bases for H. ducreyi virulence and the molecular and cellular host-pathogen interactions that result in chancroid development are not well-defined. The goal of this proposal is to test the hypothesis that the recently discovered Cu/Zn superoxide dismutase (Cu/Zn SOD) secreted by H. ducreyi is involved in bacterial defense against neutrophil killing and plays a role in the development of the unique lesions associated with chancroid disease. In vitro experiments comparing the resistance of wild- type and Cu/Zn SOD-deficient mutant H. ducreyi to paraquat- or neutrophil-generated superoxide radicals will be performed. Cu/Zn SOD mutant and wild type strains will also be compared on the basis of bacterial survival in an in vivo (swine) model of H. ducreyi infection. Observations of lesions produced by wild type and Cu/Zn SOD-deficient strains will be made in order to assess the possible contribution of SOD in chancroid lesion development.
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