FHA-LIKE PROTEIN OF HAEMOPHILUS DUCREYI

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Chancroid is a sexually transmitted disease caused by the fastodious bacterium Haemophilus ducreyi. I have identified a segment of H. ducreyi genomic DNA encoding a protein with 43% similarity to the filamentous hemagglutinin (FHA) of Bordetella pertussis; this protein can be detected in H. ducreyi cultre supernatants. I proposed to use a combination of molecular gentics, immunoelectron microscopy, adherence studies, and in vivo virulenc teting to investigate the role of this H. ducreyi FHA-like protein in the pathogenesis of chancroid. 1) A primary goal of this project is to identify, clone, and sequence the complete gene encoding the H. ducreyik FHA-like protein and to determine whether H. ducreyi contains a second gene encoding and FHA-like protein. 2) The cellular location of this putative adhesin will be determine adn the potential for processing of a precursor into a mature form will be investigated. 3) Isogenic H. ducreyi mutants deficient in the production of the FHA-like proteins (s) will be constructed and tested for their abilities to bind to several different human cell lines and extracellular matrix components. 4) These mutants wil also be evaluated in both the temperature-dependent rabbit and experimental human models of chancroid to determine the involvment of the FHA-like protein in virulence expression by H. ducreyi.