PU Prof Targets Hospital-Acquired Infection

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Seleem says repurposing an existing drug is much less costly than developing a new drug. Seleem says repurposing an existing drug is much less costly than developing a new drug.

Among hospital-acquired infections, MRSA gets most of the attention, says a Purdue University researcher; this leaves the second most common hospital-acquired infection lurking in the shadows. Vancomycin-resistant enterococci (VRE), similar to MRSA, is characterized by its antibiotic resistance, making it especially dangerous and difficult to treat. However, Purdue College of Veterinary Medicine Microbiology Professor Dr. Mohamed Seleem aims to pull VRE from the shadows and battle the disease with increased speed.

Determined to swiftly find a new treatment for VRE, Seleem is taking a somewhat unique approach, using existing, repurposed drugs, rather than relying on antibiotics.  

“This drug can move to the market very quickly; it doesn’t require extensive study, because it’s already been approved in humans. All we have to do is change its application for how it’s being used,” says Seleem. “The problem is finding the right drug that kills the right bacteria.”

Hard-to-kill bacteria is the defining trait of hospital-acquired infections such as VRE. Enterococci is a bacteria everyone has in their intestine, but in hospital settings, it can lead to infection when the microorganism escapes the intestine. Enterococci can enter the bloodstream and cause infections in the blood or in any organ. Due to extensive use of the antibiotic Vancomycin to treat the infections, the bacteria has become resistant to the drug—hence its name: Vancomycin-resistant enterococci. As is often the case with hard-to-treat infections, doctors give patients two antibiotics simultaneously.

“That has a huge impact on your normal bacteria in the gut; that by itself will lead to another problem—you get another infection with another bacteria. Your immune system will be impacted, because your normal gut is impacted,” says Seleem. “The idea of [my] research is to find an antibiotic that can remove or kill VRE without impacting your good bacteria.”

Boosted by a recent $2.5 million National Institutes of Health grant, Seleem is uncovering existing drugs that could treat VRE. In addition to speeding the process of moving the drug—repurposed for a different disease—to market, Seleem says relying on existing drugs is much less costly. Experts estimate the total cost of discovering a new drug and moving it from the lab to commercialization is a hefty $2 billion.

“Secondly, it’s a safer approach than just finding a drug from scratch. [Existing] drugs have been used in humans already, and we know everything about them—their side effects and how they’re being used,” says Seleem. “We understand these drugs, and some of them—like the one we discovered—has already been on the market for more than 50 years.” 

In fact, Seleem’s research has uncovered multiple existing drugs that also have anti-microbial activity; interestingly, the drugs are currently used to treat glaucoma and altitude sickness.

“We were lucky, actually, because we found not just one, but six drugs that are related,” says Seleem. “These drugs, specifically, kill VRE and nothing else. They don’t impact your good gut bacteria, and they have very potent activity against VRE.”

Seleem’s next steps focus on making the drug more potent; collaborating with Purdue Medicinal Chemistry and Molecular Pharmacology Assistant Professor Dr. Daniel Flaherty, the team modified the drug to make it 600 times more potent than the original formula. Pre-clinical trials will be the next step, and if successful, clinical trials could open the door to a new weapon against VRE.

“We’ve been working with many drugs, and this is one of the most exciting drugs we have so far, because we believe it has so much potential to move to the market very soon,” says Seleem. “This is something every researcher looks forward to; it’s a big, exciting thing in my field.”

Seleem says repurposing existing drugs involves analyzing drugs’ targets.
Seleem, a professor in the Purdue College of Veterinary Medicine, says his research relies on the One Health approach, which emphasizes how animals and the environment impact human health.
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