Wayne State University researchers use drug reuse to treat resistant bacterial eye infection – Medical School News

Ashok Kumar, PhD, left, and Susmita Das, PhD.

Researchers from the Department of Ophthalmology, Visual and Anatomical Sciences at Wayne State University School of Medicine have identified three non-antibiotic drugs that can protect the eye from severe inflammation during a bacterial infection. Medications may also be used as adjunctive therapy with standard antibiotics to reduce the outcome of infection.

The study was led by Ashok Kumar, PhD, associate professor of ophthalmology and visual and anatomical sciences and principal investigator at the Kresge Eye Institute. His lab has been involved in investigating host-pathogen interactions and novel treatment options in bacterial, viral, and fungal eye infection models for several years.

“One way to identify new drugs for any disease involves drug reuse, where we can identify additional uses for already approved drugs, allowing for a faster and cheaper transition from bench to bed,” said Dr. Kumar.

Susmita Das, Ph.D., Postdoctoral Fellow in Dr. Kumar’s lab, is lead author on “Transcriptional biology and systems identifies non-antibiotic drugs to treat bacterial eye infectionsPublished in iScience, a Cell Press magazine.

Post-operative eye infections are a major concern among ophthalmologists, as they can lead to potential blindness if not treated promptly. One of the most common infections after eye surgeries is endophthalmitis caused by Staphylococcus aureus, in which bacteria from the outside gain access to the inside of the eye.

“Current management of this complication involves treatment with topical or systemic antibiotics, which efficiently kill the microbe but do little to reduce inflammation,” said Dr. Kumar. “But, about 50% of these infections are also caused by various strains of antibiotic-resistant bacteria, predisposing patients to treatment failure and vision loss.”

In their search for alternative therapies to treat eye infections, they have used high-throughput techniques of transcription to understand the genome-wide changes 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. .

Working with study collaborator Manoj Basin, PhD, of Emory University in Atlanta, Georgia, who has performed in silico studies, including CMap analyses, the team predicted the three drugs that reversed the genetic signatures of bacterial endophthalmitis in the retina of an animal model. Diqualinium chloride, clophyllum tosylate, and glibenclamide.

The study team tested the efficacy of the drugs and revealed that all of them showed anti-inflammatory properties against sensitive and antibiotic-resistant bacterial strains in human retinal cells.

“We were excited to discover that while intravitreal injections of all drugs reduced intraocular inflammation even in the eyes of MRSA-resistant mice, DC and CT were able to reduce bacterial burden as well. Pharmacological therapies improve function,” Dr. Das said. and protects the eye from the death of retinal cells.

“We also wanted to verify disease outcome after adjuvant treatment of these drugs with existing antibiotic therapy during eye infection and found that these drugs showed synergism with vancomycin in improving disease severity,” said Dr. Kumar. “We are currently studying the mechanisms underlying the antimicrobial and anti-inflammatory properties of these drugs and testing their efficacy against other bacterial pathogens in order to elucidate the drug-host-microbe crosstalk.”

The work was supported by NIH grants to Dr. Kumar (R21AI135583, R01EY026964, and R01EY027381).