EXTRACELLULAR VIRULENCE FACTORS OF HAEMOPHILUS DUCREYI

描述（改编自申请人摘要）：软下疳，一种生殖溃疡 由苛养革兰氏阴性细菌杜克雷嗜血杆菌引起的疾病， 是人们最不了解的性传播疾病之一。协会 生殖器溃疡疾病和人类免疫缺陷病毒的传播之间的关系 病毒使得软下疳的控制和预防成为公共卫生问题。这 研究项目涉及两组H。杜克雷伊蛋白 它们的共同点是它们被释放到培养上清液中 并有可能影响宿主-寄生虫的相互作用， 软下疳第一组蛋白质是两个非常大的大分子， 命名为LspA 1和LspA 2，其有助于H.杜克雷伊托 抵抗正常人血清的杀伤此外，LspA 1影响毒力 表达H。ducreyi在动物模型中的作用， 血清抵抗另一组蛋白质由cdtABC基因编码 簇并包含具有细胞毒性的细胞致死膨胀毒素（CDT 体外抗人上皮细胞、人角质形成细胞的活性， 人类T细胞在第一个具体目标中，PI将确定分子 LspA 1如何影响H. ducreyi an how both LspA 1和LspA 2影响该病原体的血清抗性。第二特定 目的将涉及成熟LspA 1和LspA 2蛋白的表征， 研究LspB蛋白是否影响它们从H. ducreyi细胞在第三个具体目标中，PI将确定H。杜克雷 调节LspA 1、LspA 2和LspB表达的基因产物 proteins.第四个具体目标需要确定组成 的H.杜克雷第五个也是最后一个具体目标将评估 LspA 1、LspA 2和CDT蛋白具有诱导抗H. ducreyi在动物模型中。

Description (Adapted from the applicant's abstract): Chancroid, a ulcerogenital disease caused by the fastidious gram-negative bacterium Haemophilus ducreyi, is one of the least understood sexually transmitted diseases. The association between genital ulcer disease and transmission of the human immunodeficiency virus makes control and prevention of chancroid a public health concern. This research project involves investigation of two sets of H. ducreyi proteins which have in common the fact that they are released into culture supernatant fluid and have the potential to affect the host-parasite interaction in chancroid. The first set of protein are two very large macromolecules, designated LspA1 and LspA2, which contribute to the ability of H. ducreyi to resist killing by normal human serum. In addition, LspA1 affects virulence expression by H. ducreyi in an animal model independent of its involvement in serum resistance. The other set of proteins is encoded by the cdtABC gene cluster and comprise the cytolethal distending toxin (CDT) which has cytotoxic activity in vitro against human epithelial cells, human keratinocytes, and human T-cells. In the first Specific Aim, the PI will determine the molecular basis for how LspA1 affects virulence expression by H. ducreyi an how both LspA1 and LspA2 affect serum resistance of this pathogen. The second Specific Aim will involve characterization of the mature LspA1 and LspA2 proteins and investigation into whether the LspB protein effects their release from the H. ducreyi cell. In the third Specific Aim, the PI will identify the H. ducreyi gene product(s) which regulates expression of the LspA1, LspA2 and the LspB proteins. The fourth Specific aim entails the determination of the composition of the H. ducreyi CDT. The fifth and final Specific Aim will evaluate the LspA1, LspA2 and CDT proteins for their ability to induce immunity against H. ducreyi in an animal model.