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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Postdoctoral Individual National Research Service Award (F32)
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Bacteriology and Mycology Subcommittee 2 (BM)
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Hitchcock, Penelope
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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Ward, Christine K; Mock, Jason R; Hansen, Eric J (2004) The LspB protein is involved in the secretion of the LspA1 and LspA2 proteins by Haemophilus ducreyi. Infect Immun 72:1874-84
Ward, Christine K; Latimer, Jo L; Nika, Joseph et al. (2003) Mutations in the lspA1 and lspA2 genes of Haemophilus ducreyi affect the virulence of this pathogen in an animal model system. Infect Immun 71:2478-86
Nika, Joseph R; Latimer, Jo L; Ward, Christine K et al. (2002) Haemophilus ducreyi requires the flp gene cluster for microcolony formation in vitro. Infect Immun 70:2965-75
Lewis, D A; Stevens, M K; Latimer, J L et al. (2001) Characterization of Haemophilus ducreyi cdtA, cdtB, and cdtC mutants in in vitro and in vivo systems. Infect Immun 69:5626-34
Ward, C K; Lumbley, S R; Latimer, J L et al. (1998) Haemophilus ducreyi secretes a filamentous hemagglutinin-like protein. J Bacteriol 180:6013-22