EVALUATION OF AN OMPP2A OMPP2B DOUBLE MUTANT IN EXPERIMENTAL HUMAN INFECTION

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。两个H. ducreyi蛋白分别命名为OmpP2A和OmpP2B，它们与其他主要的孔蛋白具有同源性。孔蛋白具有重要的抗原决定因子，提供膜稳定性，并影响抗生素敏感性（1-3）。孔蛋白是人类杀菌抗体的靶标(4)。本研究的目的是验证OmpP2A OmpP2B双突变体与其等基因亲本相比感染人类皮肤的能力受损的假设。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。这些研究将确定是否OmpP2A和OmpP2B的表达是杜氏嗜血杆菌引起脓疱的必要条件，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. Two H. ducreyi proteins, named OmpP2A and OmpP2B, have homology with other major porin proteins. Porins bear important antigenic determinants, provide membrane stability, and influence antibiotic susceptibility (1-3). Porins are targets of human bactericidal antibodies (4). The purpose of this study is to test the hypothesis that an OmpP2A OmpP2B double 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 OmpP2A and OmpP2B is required for H. ducreyi to cause pustules, and may provide a rationale to develop a vaccine against H. ducrey