Adherence and Colonization in Keratitis

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DESCRIPTION: It is estimated that approximately 30,000 cases of microbial keratitis occur annually in the U.S. and 100,000 cases globally. Non-surgical trauma and contact lens wear are the leading predisposing risk factors for microbial keratitis. The mechanisms that predispose patients to keratitis as the result of extended contact lens wear remain the subject of controversy. Contact lens induced hypoxia has been used to explain the ocular complications associated with contact lens wear. However, highly oxygen permeable lenses have been introduced, but do not appear to significantly reduce the complication rate. The non-specific decrease in corneal epithelial barrier function may be mechanical in origin, stemming from the accumulation of debris underneath the contact lens during closed-eye wear, and friction and pressure from normal blinking during open eye wear. Irrespective of the trigger, microbes display enhanced adherence to wounded cornea. The mechanisms of adherence, the fate of adherent microbes, the response of epithelial cells, or the role of specific bacterial factors responsible for adherence and colonization are only now emerging for a leading cause of keratitis, namely that caused by S. aureus. We therefore propose to conduct experiments to test the following hypotheses: 1) that S. aureus uses specific matrix- or cell surface- binding proteins to bind exposed epithelial cell surfaces, or deposited extracellular matrix proteins, at the site of a wound; 2) that pathogenic lineages expressing certain constellations of traits, possibly colonization traits including biofilm formation, are enriched among keratitis isolates; and 3) that the expression of toxins by S. aureus deranges an otherwise finely balanced innate host response, rendering it inefficient and thereby allowing S. aureus to colonize and infect.