Bacterial Invasion and Trafficking within the Bladder

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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.