Surface proteins in pneumonic plague

肺鼠疫中的表面蛋白

• 批准号: 6813364
• 负责人: SUSAN C STRALEY
• 金额: $ 29.46万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6813364
• 关键词: Yersinia pestis; Yersinia pestis disease; bacterial capsules; bacterial genetics; bioinformatics; biotechnology; bioterrorism /chemical warfare; gene expression; laboratory mouse; lung; mass spectrometry; membrane proteins; molecular probes; protein quantitation /detection; proteomics; technology /technique development; vaccine development

DESCRIPTION (provided by applicant): Yersinia pestis is the most highly virulent extracellular pathogen known and poses an ominous threat as an agent of bioterrorism. The bacteria are highly infectious by aerosol and cause pneumonic plague, which can kill in as little as two days after exposure. There is no vaccine available for plague. Vaccines under development for prevention of plague contain two proteins called LcrV and FI. They provide moderate protection against pneumonic plague, but not if the infecting strain lacks the F1 capsular protein. F1 is not required for virulence by the aerogenic route, and its gene is easily deleted, posing the potential of a weaponized Fl-lacking strain against which these candidate vaccines do not protect effectively. To find alternative vaccine candidates, we will develop a novel proteomics approach to identify Y. pestis surface proteins that are expressed during pneumonic plague. These studies will provide the technical base for a more detailed screen for new plague vaccine candidates. Further, we hope that one or more of the proteins we identify in the proposed pilot studies will prove in the future to be protective against pneumonic plague caused by a non-encapsulated strain against which vaccines currently under development will not protect adequately. Our aims are: 1. Develop a biotinylation-MS approach for identification of surface-exposed proteins on Y. pestis recovered from lungs of mice with pneumonic plague. 2. Identify up to 10 surface proteins and evaluate them for conditions that optimize expression.

描述（由申请人提供）：耶尔森氏菌是已知的最高度毒性的细胞外病原体，并作为生物恐怖剂构成了不祥的威胁。细菌具有气溶胶高度感染力，并引起肺鼠疫，暴露后两天可能会杀死。没有可用于鼠疫的疫苗。预防鼠疫的开发疫苗包含两种称为LCRV和FI的蛋白质。它们提供了适度的针对肺炎鼠疫的保护，但如果感染菌株缺乏F1囊蛋白。通过充气途径毒力不需要F1，其基因很容易被删除，从而构成了这些候选疫苗无法有效保护的武器化FL菌株的潜力。为了找到替代疫苗候选物，我们将开发一种新型的蛋白质组学方法，以鉴定鼠疫表面蛋白质在肺鼠疫期间表达。这些研究将为新的瘟疫疫苗候选者提供更详细的屏幕提供技术基础。此外，我们希望我们在拟议的试点研究中鉴定出的一种或多种蛋白质将来会证明是针对由未封闭的菌株引起的肺炎瘟疫的保护性，目前正在开发的疫苗将无法充分保护该疫苗。我们的目的是：1。开发一种生物素化-MS方法，用于鉴定从患有肺炎鼠疫的小鼠肺中回收的鼠疫处的表面暴露蛋白。 2。识别多达10种表面蛋白，并评估它们的优化表达条件。