Functional characterization of the periplasmic chaperone SurA and analysis of its role in the virulence of uropathogenic Escherichia coli

大肠杆菌β-桶外膜蛋白的周质分子伴侣SurA在外膜完整性和细胞被膜稳态中起着至关重要的作用。此外，SurA是泌尿系致病性大肠杆菌完全毒力所必需的。大肠杆菌（UPEC）膀胱炎菌株UTI 89。缺乏SurA干扰粘附性1型菌毛的正常生物发生，这是膀胱炎中的一个重要定植决定因素。然而，也有证据表明，这种保守的分子伴侣对尿路致病性的影响更为复杂。UPEC是一组异质性分离株，其毒力因子的库和表达水平差异很大，并导致不同严重程度和定位的尿路感染。通过分析不同UPEC分离株的surA突变体，包括研究充分的肾盂肾炎菌株E. coli 536和CFT 073中，我们已经鉴定出受SurA影响的其他毒力相关性状。为了更全面地了解SurA如何影响UPEC的毒力，我们现在试图鉴定与疾病病因相关的蛋白质，这些蛋白质受SurA影响，使用蛋白质组学方法与进一步的表型分析互补，并研究其多效性效应的分子基础。此外，我们将研究SurA对肾盂肾炎相关UPEC的毒力潜力的影响，在体外和体内使用细胞培养和小鼠感染模型。

The Escherichia coli periplasmic chaperone SurA for β-barrel outer membrane proteins plays a crucial role in outer membrane integrity and cell envelope homeostasis. In addition, SurA is required for full virulence of the uropathogenic E. coli (UPEC) cystitis strain UTI89. Lack of SurA interferes with the proper biogenesis of the adhesive type 1-fimbriae, an essential colonization determinant in cystitis. However, there is also evidence that the influence of this conserved chaperone on uropathogenicity is more complex. UPEC are a heterogeneous group of isolates that differ considerably in their repertoire and expression levels of virulence factors and cause urinary tract infections of varying severity and localization. By characterizing surA mutants of different UPEC isolates, including the wellstudied pyelonephritis strains E. coli 536 and CFT073, we have already identified additional virulence-associated traits that are affected by SurA. To gain a more complete understanding on how SurA contributes to UPEC virulence, we now seek to identify proteins relevant to disease causation that are affected by SurA using proteomic approaches complementary to further phenotype analysis as well as to examine the molecular basis of its pleiotropic effects. In addition, we will study the influence of SurA on the virulence potential of pyelonephritis-associated UPEC both in vitro and in vivo using cell culture and mouse infection models.