SIGNIFICANCE OF CORNEAL CELL INVASION BY BACTERIA

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DESCRIPTION (Adapted from applicant's abstract): Pseudomonas aeruginosa can cause sight-threatening corneal infection. The emergence of multiple antibiotic resistance to this organism suggests that new approaches are needed for control of Pseudomonas aeruginosa infections. In previous studies, the investigator has demonstrated that invasive Pseudomonas aeruginosa strains can invade corneal epithelial cells, break out of the endocytic vacuole, replicate within these cells, and eventually they kill the host cell. The long-term goal of this project is to determine if blocking corneal cell invasion by Pseudomonas aeruginosa could be used for therapeutic or preventative intervention. To determine the mechanisms involved in bacterial invasion and their role in disease, the following hypothesis will be tested: specific bacterial genes modulate Pseudomonas aeruginosa invasion and internalization of this pathogen involves exploitation of host cell focal adhesion complex (FAC) signaling. Specific aim 1 is to identify specific bacterial genes that modulate Pseudomonas aeruginosa invasion, and to test the virulence of mutants and/or transconjugants that are altered in their ability to invade in vivo. Specific aim 2 is to determine the role of FAC signaling in invasion in vitro and in vivo. The proposed studies will provide new insight into the mechanisms of corneal cell invasion by Pseudomonas aeruginosa and of the role of invasion in disease, which could lead to new strategies for treating Pseudomonas aeruginosa ocular and non-ocular infections.