ONLINE EXCLUSIVE

October 2022

by Liz Hillman
Editorial Co-Director

Research out of Wayne State University turned to “drug repurposing” to identify already-approved therapies that could be used to treat antibiotic-resistant bacterial infections in the eye.

The investigation, led by Ashok Kumar, PhD, within the university’s Department of Ophthalmology, Visual and Anatomical Sciences, ultimately identified three non-antibiotic drug candidates that had anti-inflammatory effects against antibiotic-sensitive and antibiotic-resistant bacterial strains in cultured human retina cells.

According to a news article from the university, post-doctoral fellow Susmita Das, PhD, said the researchers used “high-throughput techniques of transcriptomics to understand the genome-level alterations involved in the host response during bacterial endophthalmitis, and adopted an innovative systems biology approach to identify key molecules and pathways associated with Staphylococcus aureus endophthalmitis.”

The team, with Emory University collaborator Manoj Bhasin, PhD, used a technique to predict three drugs that could reverse the genetic signatures of bacterial endophthalmitis, identifying dequalinium chloride, clofilium tosylate, and glybenclamide.

Researchers then tested them in vivo in mouse eyes with methicillin-resistant staph infections. Dr. Das said that dequalinium chloride and clofilium tosylate reduced bacterial burden.

“Drug treatments improved visual function and protected the eye from retinal cell death,” Dr. Das told the university.

“We also wanted to check the outcome of the disease following an adjunct therapy of these drugs with the existing antibiotic treatment during ocular infection and found that these drugs demonstrated synergy with vancomycin in improving disease severity,” Dr. Kumar said.

In terms of using a drug-repurposing technique to identify these possible therapies, Dr. Kumar said in the article that finding already-approved drugs provides the “quickest and cheapest possible transition from bench to bedside.”

The team is conducting more studies to better understand the mechanism of action of these drugs against these microbes and against other bacterial agents. The research is published in the journal iScience.¹

Reference

1. Das S, et al. Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection. iScience. 2022;25:104862.