Secretion systems for anti-malarial bacterial strains

抗疟疾菌株的分泌系统

• 批准号: 7155359
• 负责人: DAVID J LAMPE
• 金额: $ 5.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155359
• 关键词: Plasmodium; bacteria; genes; human; malaria; proteins; secretion

DESCRIPTION (provided by applicant): Malaria is a major human disease that has shown no evidence of declining despite years of drug therapy to treat infected humans and efforts to control its mosquito vectors. Alternative strategies to deal with this problem are clearly needed. Work has progressed in the area of antimalarial effector genes that can prevent the establishment of Plasmodium parasites in their mosquito hosts, but there is currently no way to deliver these genes and their products to mosquitoes in the wild. One method to deliver such genes is by transforming bacteria that normally live in mosquito midguts, like the gamma proteobacterium Enterobacter agglomerans, into gene product delivery vehicles. This proposal seeks to tackle one aspect of modifying E. agglomerans into an effective antimalarial reagent, namely the development of efficient protein secretion systems for this bacterium and the testing of these systems to determine whether E. agglomerans that secrete antimalarial proteins can block the transmission of malaria from mosquitoes to their hosts in a rodent malaria model system. Both Type I and Type II secretion systems will be developed and tested.

描述（由申请人提供）：疟疾是一种主要的人类疾病，尽管多年来对受感染的人进行药物治疗并努力控制其蚊子媒介，但没有证据表明其下降。显然需要采取其他战略来处理这一问题。在抗疟疾效应基因领域的工作已经取得了进展，这些基因可以防止疟原虫寄生虫在蚊子宿主中建立，但目前还没有办法将这些基因及其产物传递给野外的蚊子。传递这些基因的一种方法是将通常生活在蚊子中肠中的细菌，如γ-变形杆菌成团肠杆菌转化为基因产物传递载体。该建议旨在解决修改E的一个方面。将成团大肠杆菌转化为有效的抗疟剂，即开发该细菌的有效蛋白分泌系统，并测试这些系统以确定E.在啮齿动物疟疾模型系统中，分泌抗疟蛋白的成团菌可阻断疟疾从蚊子向其宿主的传播。将开发和测试I型和II型分泌系统。