Bacterial Invasion and Trafficking within the Bladder

描述(申请人提供)：尿路致病性大肠埃希菌(UPEC)是尿路感染(UTIs)的主要病原体。UPEC分离株能够在尿路内的宿主细胞和组织内瞬时入侵、生存和繁殖。这可能对UPEC有效定植尿路的能力至关重要，并可能促进膀胱内长期、低水平感染的建立。这种亚临床感染可能是反复发作的急性尿路感染的来源，这种感染困扰着许多人的一生。这项建议的主要目标是确定UPEC能够进入膀胱上皮细胞、持续、增殖并最终重新出现的机制。利用细胞培养和小鼠尿路感染模型系统，将确定UPEC进入膀胱上皮细胞所利用的宿主受体和信号通路。宿主肌动蛋白细胞骨架调节UPEC复制和重新出现的能力将被确定。此外，还将评估UPEC劫持宿主细胞泡囊运输和分选机械的能力。这项研究将提供对尿路感染的更多了解，目前尿路感染是最常见的细菌感染之一，并将有助于开发更有效的抗菌疗法。

DESCRIPTION (provided by applicant): Strains of uropathogenic Escherichia coli (UPEC) are the primary causative agents of urinary tract infections (UTIs). UPEC isolates are able to transiently invade, survive and multiply within host cells and tissues within the urinary tract. This is potentially critical to the ability of UPEC to effectively colonize the urinary tract and may promote the establishment of long-term, low-level infections within the bladder. Such sub-clinical infections may serve as a source for the recurrent acute UTIs that plague many individuals throughout their lives. The primary objectives of this proposal are to define the mechanisms by which UPEC is able to move into the bladder epithelium, persist, multiply and eventually reemerge. Using cell culture and mouse UTI model systems, the host receptors and signaling pathway utilized by UPEC for entry into bladder epithelial cells will be defined. The capacity of the host actin cytoskeleton to modulate UPEC replication and reemergence will be determined. In addition, the ability of UPEC to highjack the host cell vesicular trafficking and sorting machinery will be assessed. This research will provide a greater understanding of UTIs, which presently rank among the most common of bacterial infections, and will contribute to the development of more efficacious antibacterial therapeutics.