聚磷酸盐激酶1在奇异变形杆菌致尿路感染中的作用及其机制研究

项目名称： 聚磷酸盐激酶1在奇异变形杆菌致尿路感染中的作用及其机制研究

项目编号： No.81200505

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 彭亮

作者单位： 广州医科大学

项目金额： 22万元

中文摘要： 奇异变形杆菌 (Proteus Mirabilis, P. Mirabilis)属于变形杆菌属，是引起泌尿道感染的重要病原菌之一。研究发现(包括我们已发表的结果)，聚磷酸盐激酶1（Polyphosphate kinase, PPK1）与某些细菌的致病性有重要关系，并参与了多个毒力基因的表达调控，然而它在P. Mirabilis乃至整个变形杆菌属的致病中扮演什么角色，目前还处于未知状态。鉴于以上情况，本项目拟构建P. Mirabilis的ppk1基因缺失株，结合体内、外模型考察ppk1在P. Mirabilis粘附、侵袭尿路上皮组织中的作用，并分析ppk1缺失对细菌群集运动能力及重要毒力因子如鞭毛、尿素酶等表达的影响。通过对上述内容的探索，我们期望明确ppk1是否与P. Mirabilis感染尿路组织相关及其可能的调控机制，从而为阐明P. Mirabilis引发尿路感染的机制打下良好基础。

中文关键词： 聚磷酸盐激酶1；奇异变形杆菌；尿路感染；基因突变；

英文摘要： Proteus mirabilis belongs to the Tribe Proteae. It is a Gram-negative, facultatively anaerobic, rod shaped bacterium, frequently found in soil, water and the intestinal tract of humans. When this organism, however, enters the urinary tract, wounds, or the lungs it can become pathogenic. Proteus mirabilis commonly causes urinary tract infections (UTI) and the formation of stones. The pathogenesis of urinary tract infections induced by P.Mirabilis still remains largely unknown. Some studies (including our research results published on the Journal of Future Microbiology recently) have suggested that polyphosphate kinase (PPK1) is an important virulence determinant in many pathogens, and exhibits potential to be an attractive target for chemotherapy due to the absence of the PPK1 homologue in mammalian cells. However, the role of PPK1 in the pathogenesis of P.Mirabilis infections is completely unknown. To solve this problem, a ppk1 isogenic in-frame ppk1 deletion mutant of P.Mirabilis strain HI4320 will be constucted and characterized in this study. The adhesion and invasion abilities to the UTI in vitro and in vivo of the mutant will be compared to those of the wild-type strain. Additionally, the effection of ppk1 deletion on the swarming motility and expression of some important virulence factors in P. Mirabil

英文关键词： Polyphosphate kinase；Proteus mirabilis；urinary tract infections；gene mutation；