EVALUATION OF AN DLTA MUTANT IN EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。杜热氏嗜血杆菌是生殖器溃疡下巴疾病的病原体。最近，Elkins及其同事描述了编码Ducreyi Lectin A的一种名为DltA的新型表面脂蛋白的基因。一种名为FX533的dltA突变体对50%的正常人血清敏感。在人类感染杜氏杆菌的挑战模型中，细菌通过穿孔伤口进入皮肤，血清渗入伤口。在人类挑战模型中，血清耐药性是一个重要的毒力决定因素。这项研究的目的是检验这样一种假设，即与其同基因的亲本相比，DltA突变体感染人类皮肤的能力受到损害。为了验证这一假设，我们将比较父母和突变人在人类受试者中导致实验性感染的能力。这些研究将确定杜氏嗜血杆菌是否需要表达DltA才能引起脓疱疮，并可能为开发杜氏嗜血杆菌疫苗提供理论基础。

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.