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Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.

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.

SUBMITTER: Das S

PROVIDER: S-EPMC9399287 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.

Das Susmita S Singh Sukhvinder S Satpathy Sarthak S Bhasin Manoj M Kumar Ashok A

iScience 20220802 9

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 <i>Staphylococcus aureus</i> (SA) infected mouse retina. The analysis predicted three non-antibiotic drugs, Dequalinium chloride (DC), Clofilium tosylate (CT), and Glybenclamide ...[more]

PMID: 36034221

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Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.

Publications

Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.

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