Purdue researchers hope to repurpose drugs to fight deadly superbugs

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Tiny bugs are stronger than big people. They can chew away at bones, skin and organs.

For decades, doctors could fight off microbes with an arsenal of antibiotics and antivirals. But after being exposed to tens of millions of doses, the bugs have adapted and become superbugs. Some of them are able to withstand almost any treatment.

Each year in the U.S., more than 2 million people get an antibiotic-resistant infection, and at least 23,000 people die, according to the Centers for Disease Control and Prevention, which calls the issue “one of the biggest public health challenges of our time.”

Now, researchers at Purdue University are exploring whether they can repurpose some drugs that have already been approved by the Food and Drug Administration for other uses.

The Purdue team recently won a $2.5 million, five-year grant from the National Institutes of Health to screen several drugs in an effort to find new ways to attack a particular variety of superbug.

“These are approved drugs, so they are safe already,” said Dr. Mohamed Seleem, professor of microbiology at Purdue.

For years, such tried-and-true antibiotics as penicillin, streptomycin and tetracycline were able to help doctors fight off microbes. But many bugs have developed a hardy resistance to them—and even to vancomycin, a powerful antibiotic that for years was considered the drug of last resort.

Today, vancomycin-resistance enterococci are to blame for more than 5% of all deaths attributed to antibiotic-resistance infection in the U.S., second only to MRSA, Purdue said.

Enterococci are bacteria that live in everyone’s intestines and genital tracts. They’re usually harmless, but can sometime cause an infection. VRE bugs are usually acquired in hospitals.

If researchers find a promising drug already on the market to treat VRE, they can skip several years of preclinical study. That’s because the drugs have already been extensively tested and researchers won’t have to repeat early-phase studies to determine such basic scientific findings as how a drug is absorbed and metabolized, or determining safe dosage levels.

Seleem plans to screen several drugs often used to treat glaucoma, called carbonic anhydrase inhibitors, to see how well they can treat VRE. In previous studies, CAIs were shown to be more effective in killing VRE than the drugs typically used to treat it. Once the drugs make it to the intestine, they’re easily absorbed into the rest of the body. But Purdue said for them to be effective in killing VRE, the drugs need to stay inside the intestine, where they have prolonged exposure to the bacteria.

The challenge, Seleem said, is finding a drug that will selectively remove the VRE and not kill other bacteria that serve a purpose in the body. He will test six pre-approved drugs against VRE.

Seleem will work with Daniel Flaherty, an assistant professor of medicinal chemistry and molecular pharmacology at Purdue.

“Hopefully within two or three years, we would have a good preclinical drug that someone or some company could take forward into clinical trials,” he said.

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