This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Haemophilus ducreyi is the etiologic agent of the genital ulcer disease chancroid. Recently, the genes corresponding to an H. ducreyi ECA (Enterobacterial Common Antigen)-like pathway, which should assemble a surface glycolipid, were identified by Munson and colleagues. The first gene in the pathway, wecA complements an E. coli wecA mutant so that it can assemble the ECA glycolipid. An H. ducreyi wecA mutant, 35000HPwecA, was constructed. When grown in vitro, 35000HPwecA, does not appear to be phenotypically different than its parent, 35000HP. Recently, the Spinola laboratory captured bacterial transcripts in pustules of human volunteers. These experiments were designed to identify transcripts that are more abundant in vivo than in vitro. Two of the transcripts that were captured from the lesions are in the H. ducreyi ECA-like pathway. It is possible that the H. ducreyi ECA-like pathway is upregulated or expressed only in vivo. The most direct way to test whether ECA-like pathway is important in H. ducreyi pathogenesis is to test an ECA-like pathway mutant in human volunteers. The purpose of this study is to test the hypothesis that 35000HPwecA is impaired in its ability to infect human skin when compared to its isogenic parent. To test this hypothesis, we will compare the ability of the parent and the mutant to cause experimental infection in human subjects. These studies will establish whether expression of wecA is required for H. ducreyi to cause pustules, and may provide a rationale to develop a vaccine against H. ducreyi.
Showing the most recent 10 out of 767 publications
