PVM Scholar Repurposes Drugs as Antimicrobial Agents for Infections

A Purdue Veterinary Medicine faculty member in the Department of Comparative Pathobiology (CPB) has developed an innovative strategy to better treat bacterial and fungal infections while also lessening the length of the drug development process, saving years of expensive research.  Associate Professor of Microbiology Mohamed Seleem leads a research team that uses novel drug repurposing methods to test if drugs already approved by the Federal Drug Administration (FDA) can have an effect on bacterial and fungal infections. The team already has discovered two drugs that have promise as potent antimicrobial agents for treating both superficial and invasive infections.

Dr. Seleem emphasized that the global health epidemic of bacterial and fungal resistance to conventional antibiotics requires immediate action. “In the United States alone more than two million individuals are stricken each year with infections caused by multidrug-resistant pathogens,” Dr. Seleem said. “Invasive fungal infections afflict millions of patients annually, resulting in nearly one-and-a-half million deaths. The demand for antifungals is at an all-time high because current antifungal treatments aren’t working very well and can't be administered very conveniently.”

While about 30 percent of drugs and vaccines newly approved by the FDA have been repurposed, Dr. Seleem said none have been tested and repurposed for use as an antifungal or antibacterial agent. His research team aims to change that by screening 3,200 of the 4,000 available approved drugs for activity against bacteria and fungi. “We take a drug that is being used for, say, heart disease and we re-use it as something like a topical ointment over the skin. The drug hasn’t changed, but the method of application and purpose has,” Dr. Seleem said. “We have ready information about the drugs from previous research for its initial purpose, but we conduct tests in the new model, since they have never been used as an antifungal or antimicrobial, to reveal any additional information we may need. We plan on buying the additional 800 drugs for testing.”

Through his research, Dr. Seleem already has identified two drugs, auranofin and ebselen, that can be repurposed as antimicrobial agents and also display antifungal mechanisms. The drugs are capable of killing intracellular Methicillin-resistant Staphylococcus aureus (MRSA), a bacterium that causes numerous difficult-to-treat infections in humans. “Through our trials we have found that these two drugs have the ability to disrupt adherent staphylococcal biofilms, the most frequent cause of infections originating in hospitals,” Dr. Seleem said. “We’ve found also that they suppress toxin production and key resentment factors and reduce excessive host-inflammatory responses associated with these toxins, significantly reducing bacterial load and enhancing wound healing.”

Besides the manifest benefits of treatment for bacterial and fungal infections, repurposing drugs for antimicrobial use outside of their current scope could benefit companies in other ways. “Repurposing existing approved drugs allows companies to bypass much of the preclinical work and early-stage clinical trials required for new compounds, thus cutting the cost associated with bringing a drug to the marketplace by as much as 40 percent,” Dr. Seleem said. “Given these drugs have already been tested in human patients, valuable information pertaining to their chemical parameters are known. This permits a better understanding of the overall pharmacology of the drug, potential routes of administration and establishing an appropriate dosing regimen for patients.”

Dr. Seleem plans to also research repurposing drugs for the treatment of acne and toenail fungus. “Approximately 85 percent of people ages 12-24 suffer from at least minor acne, and current treatments aren’t always effective. Toenail fungus is prevalent in about 10 to 20 percent of the world population, and current treatment, which can take up to three years, is only effective in about 10 percent of those people,” he said. “So we want to start screening the causative agent of these conditions and hopefully find a treatment that is safe and effective that is already being used in other approved drugs to fast-track its availability to the market.” 

Dr. Seleem’s innovation is patented through the Purdue Research Foundation Office of Technology Commercialization. The research has been funded by startup and university incentive grants, as well as a one-year, $250,000 grant from the National Institutes of Health. Dr. Seleem is seeking additional funding to expand his research, and also is open to partnerships with companies that could use his research to move a drug into clinical trials for its new purpose.

Children’s Book Series Spotlights Veterinary Heroes like Dr. Seleem

Not only is Dr. Mohamed Seleem a veterinarian-scientist conducting groundbreaking research as a PVM associate professor of microbiology, he also is a role model for children who could one day follow in his footsteps as future veterinarians.  That’s why Dr. Seleem is prominently featured in a new children’s book entitled “Macaws Need Medicines, Too!” published as part of a Purdue Veterinary Medicine led program supported by the Science Education Partnership Award (SEPA) program of the National Institutes of Health.  Called This is How We “Role”, the PVM-led program aims to increase elementary school students’ awareness of the vital role veterinarian-scientists play in keeping people healthy.  The book featuring Dr. Seleem is the latest in a series published as part of the program.  Each work highlights a different veterinarian-scientist and is printed in both English and Spanish.

This story is part of the 2016 Annual PVM Report.

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