Corneal infection is often the result of injury or improper contact lens hygiene practices, both of which compromise epithelial health and barrier function. To infect epithelial cells, Pseudomonas aeruginosa typically uses enzymes produced by type three secretion system (T3SS) to disrupt adhesion and cause cytotoxicity. One of the T3 secreted effector toxins, ExoS, has domain with broad substrate specificity, including targets that remain to be identified. In this study, we will determine ExoS substrates in corneal epithelial cells which will deepen our understanding of bacterial cornea interactions.

Infectious keratitis is the fifth leading cause of blindness globally, with mild cases leading to vision impairment and severe cases leading to ocular scarring and permanent blindness. The proposed study will investigate persistence of the conditionally intracellular gram-negative bacterium, Pseudomonas aeruginosa, regarding a bacterial metabolic and virulence shift within subcellular corneal epithelial cell niches. Success of this study will advance the field with understanding and potential avenues to study, control, and eradicate persistent bacterial populations of the ocular surface and other epithelial barriers.

Bacteria such as Pseudomonas aeruginosa (Pa) can cause an infection called infectious corneal keratitis that can lead to permanent vision loss or blindness. This occurs when Pa passes through corneal surface cells and deeper into the corneal tissue. The events leading up to and following a corneal keratitis infection are fairly well understood, however the early response and detection of Pa by corneal epithelial cells (CECs) remain understudied. It is, however, known that CECs play an active role in preventing corneal infections. This project will investigate how CECs detect and respond to Pa and how these responses protect from infection.