EVALUATION OF AN DLTA MUTANT IN EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。杜氏嗜血杆菌是生殖器溃疡软下疳的病原。最近，Elkins和他的同事描述了一种名为Ducreyi凝集素a的新型表面脂蛋白DltA的编码基因。一种名为FX533的dltA突变体对50%的正常人血清的杀伤能力敏感。在杜克雷伊希氏杆菌感染的人体攻击模型中，细菌通过穿刺伤口进入皮肤，血清转运到伤口中。在人感染模型中，血清耐药性是一个重要的毒力决定因素。本研究的目的是验证一种假设，即与等基因亲本相比，DltA突变体感染人类皮肤的能力受损。为了验证这一假设，我们将比较亲本和突变体在人类受试者中引起实验性感染的能力。这些研究将确定杜氏嗜血杆菌是否需要表达DltA才能引起脓疱，并可能为开发针对杜氏嗜血杆菌的疫苗提供依据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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 gene encoding a novel surface lipoprotein called DltA for Ducreyi Lectin A was described by Elkins and colleagues. A dltA mutant, called FX533, was susceptible to killing by 50% normal human serum. In the human challenge model of H. ducreyi infection, bacteria are introduced into the skin via puncture wounds, and serum transudates into the wounds. Serum resistance is an important virulence determinant in the human challenge model. The purpose of this study is to test the hypothesis that a DltA mutant 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 DltA is required for H. ducreyi to cause pustules, and may provide a rationale to develop a vaccine against H. ducreyi.