# Genomic evidences based novel therapy for Staphylococcal infections

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2020 · $244,054

## Abstract

Project Summary
Staphylococcus aureus (SA) accounts for 16% of all hospital-acquired infections (HAIs) and is responsible for
more deaths in the U.S. annually than HIV/AIDS. The pathogen’s high morbidity and mortality are in part
attributable to the fact that SA has developed resistance to many currently available antibiotics. Thus, there is
an urgent need to discover/develop new therapeutic agents. Using an ocular staphylococcal infection models
and an innovative genomic-based drug repurposing approach, we identified three drugs, Dequalinium Chloride
(DC), Clofilium Tosylate (CT), and Glibenclamide (GLB), which can combat SA infection by modulating the
genes/pathways activated during infection. Indeed, our in vitro preliminary studies revealed that both DC and
CT exhibit direct bactericidal activities against SA and S. epidermidis (SE). Moreover, two drug combinations
significantly reduced the expression of common inflammatory mediators, including IL-1β and TNF-α, in SA-
challenged microglia, indicating the potential therapeutic effects of these drugs in staphylococcal infections.
Studies outlined in the current proposal will evaluate the therapeutic efficacy of these novel drugs in vivo. In
Aim-1, we will determine the therapeutic efficacy of novel drugs in mouse models of staphylococcal
endophthalmitis. This will be accomplished by administering the drugs in two combinations, DC+GLB and
DC+CT, at various times points post SA or SE infection in B6 mouse eyes. The drugs will also be tested in
combination with the conventional antibiotic, vancomycin. The experiments will also examine the ocular toxicity
of the drug combinations. Disease outcome will be measured by assessing bacterial burden, levels of
inflammatory mediators, retinal tissue damage, and retinal function testing. Aim-2 is designed to investigate the
molecular mechanisms underlying the therapeutic effects of the novel drugs and compare their modes of
action with antibiotics. The proposed experiments include the administration of the best drug combination and
a comparison of its therapeutic efficacy with that of vancomycin, followed by a comparative transcriptome and
systems biology analysis of antibiotic vs. drug treated retinal tissue. Given the need for new anti-microbial
therapeutic agents and the attractive features of drug repurposing, this study has considerable potential to
develop novel therapies for both ocular and non-ocular staphylococcal infections.

## Key facts

- **NIH application ID:** 9972857
- **Project number:** 5R21AI140033-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Manoj Bhasin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $244,054
- **Award type:** 5
- **Project period:** 2019-07-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972857

## Citation

> US National Institutes of Health, RePORTER application 9972857, Genomic evidences based novel therapy for Staphylococcal infections (5R21AI140033-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972857. Licensed CC0.

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