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）：鼠疫耶尔森氏菌是已知毒性最强的细胞外病原体，作为生物恐怖主义的媒介构成了不祥的威胁。这种细菌通过气溶胶具有高度传染性，并引起肺鼠疫，接触后短短两天内即可死亡。没有针对鼠疫的疫苗。正在开发的用于预防鼠疫的疫苗含有两种称为 LcrV 和 FI 的蛋白质。它们对肺鼠疫提供中等保护，但如果感染菌株缺乏 F1 荚膜蛋白，则不能提供保护。 F1 并不是通过气源途径产生毒力所必需的，而且它的基因很容易被删除，从而有可能成为武器化的缺乏 F1 的菌株，而这些候选疫苗无法有效地预防这种菌株。为了寻找替代候选疫苗，我们将开发一种新的蛋白质组学方法来鉴定在肺鼠疫期间表达的鼠疫耶尔森氏菌表面蛋白。这些研究将为更详细地筛选新的鼠疫候选疫苗提供技术基础。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能够证明能够预防由非封装菌株引起的肺鼠疫，目前正在开发的疫苗无法充分预防这种鼠疫。我们的目标是： 1. 开发一种生物素化-MS 方法，用于鉴定从患有肺鼠疫的小鼠肺部回收的鼠疫耶尔森氏菌的表面暴露蛋白。 2. 鉴定最多 10 种表面蛋白并评估它们的优化表达条件。