Abstract
Increasing antibiotic resistance among ocular pathogens often results in treatment failure for blinding infections such as endophthalmitis. Hence, newer therapeutics is needed to combat multidrug-resistant infections. Here, we show a drug repurposing approach using a connectivity map based on temporal transcriptomics of Staphylococcus aureus (SA) infected mouse retina. The analysis predicted three non-antibiotic drugs, Dequalinium chloride (DC), Clofilium tosylate (CT), and Glybenclamide (Glb) which reversed the SA infection signatures. Predicted drugs exhibited anti-inflammatory properties in human retinal cells against sensitive and resistant strains of SA. Intravitreal administration of all drugs reduced intraocular inflammation in SA-infected mouse eyes while DC and CT also reduced bacterial burden. Drug treatment improved visual function coinciding with reduced Caspase-3 mediated retinal cell death. Importantly, all drugs exhibited synergy with vancomycin in improving disease outcomes. Overall, our study identified three non-antibiotic drugs and demonstrated their therapeutic and prophylactic efficacies in ameliorating intraocular bacterial infection.