EVALUATION OF AN WECA MUTANT IN EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS

人类嗜血杆菌感染实验中 WECA 突变体的评估

• 批准号: 7717569
• 负责人: Stanley M. Spinola
• 金额: $ 0.01万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717569
• 关键词: Complement; Computer Retrieval of Information on Scientific Projects Database; Disease; Escherichia coli; Evaluation; Funding; Genes; Genital system; Glycolipids; Grant; Hemophilus; Hemophilus ducreyi; Human; Human Volunteers; In Vitro; Infection; Institution; Laboratories; Lesion; Parents; Pathogenesis; Pathway interactions; Purpose; Research; Research Personnel; Resources; Skin; Source; Surface; Testing; Transcript; Ulcer; United States National Institutes of Health; Vaccines; design; enterobacterial common antigen; human subject; in vivo; mutant; research study

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 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 杜克雷嗜血杆菌是生殖器溃疡性疾病软下疳的病原体。 近年来，H. ducreyi ECA（肠杆菌共同抗原）样途径，其应组装表面糖脂，由Munson及其同事鉴定。 途径中的第一个基因wecA与E. coliwecA突变体，使其能够组装ECA糖脂。 一个H。构建了ducreyi wecA突变体35000 HPwecA。 当在体外生长时，35000 HPwecA似乎与其亲本35000 HP没有表型差异。 最近，Spinola实验室在人类志愿者的脓疱中捕获了细菌转录本。 这些实验旨在鉴定体内比体外更丰富的转录物。 从病变中捕获的两个转录本在H。ducreyi ECA样途径。 可能是H. ducreyi ECA样途径仅在体内上调或表达。 检测ECA样通路在H。ducreyi发病机制的目的是测试人类志愿者中的ECA样途径突变体。 本研究的目的是检验35000 HPwecA与其同基因亲本相比感染人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wecA的表达是否是H. ducreyi引起脓疱，并可能提供一个理论基础，开发疫苗，针对H。ducreyi。