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CU Boulder Researcher Working to Give New Life to Old Drugs Fighting Superbugs

September 27, 2018

University of Colorado Professor Corrie Detweiler is leading research to once again make antibiotic-resistant "superbugs" vulnerable to treatment.

A University of Colorado scientist is leading research aimed at making bacteria that have become resistant to some drug treatments vulnerable once again to treatment.

Antibiotic-resistant “superbugs” now infect 2 million people per year, and with a lack of new medications being developed to treat them, Corrie Detweiler, a CU professor of molecular, cellular and developmental biology — along with her colleagues — is taking a new approach to make existing drugs more effective against their targets.

“We started, really in the heart of basic science, which is just trying to understand how bacteria like salmonella can survive inside of mammalian cells, inside of our cells,” Detweiler said.

“We got the idea that maybe we could use what we knew to screen for new chemicals that can prevent bacteria from replicating inside of mamallian cells,” she said. “And so we did that, and we found a bunch of compounds, and those we have so far been able to follow up on look like they could be useful.”

According to a CU news release concerning the study on which Detweiler is lead author, more than 23,000 people die each year in the United States as a result of bacterial infections that have evolved to resist antibiotics. Many more suffer from life-threatening bouts with ailments such as pneumonia and urinary tract infections that once were easily treatable. Additionally, some forms of gonorrhea and tuberculosis now resist all available drugs. Detweiler sees the potential that, absent intervention, society could revert to a period 200 years ago when a minor infection could mean death.

This spurred her laboratory’s investigation into exploration of ways to home in on compounds that would inhibit bacteria from replicating inside the host cell, without harming the host. Their strategy is to get inside the bacteria and turn off the cellular mechanisms known as efflux pumps, which bacteria use to shield themselves from both antibiotics and the body’s natural immune boosting proteins.

“Bacteria are really smart, and they have learned to use these pumps to pump out whatever we throw at them to kill them, so they can live happily,” Edward Yu, a professor of pharmacology at Case Western Reserve University who collaborated with Detweiler on the research, said in a statement. “The compounds Corrie is working on inhibit those pumps.”

Detweiler has developed a new technique called SAFIRE, which is being used to screen for new molecules that possess anti-microbial properties. SAFIRE makes use of pioneering cell-imaging techniques to study what the compounds do to mammalian cells that have been infected with bacteria for more than 18 hours.

That method has allowed Detweiler’s lab to quickly filter out toxic compounds, and focus quickly — from a pool more 14,400 potential candidates screened — on at least three that are thought to have strong potential.

“What we’re doing now is, in collaboration with a Boulder company called Crestone Pharma Inc., what they are doing for us is the medicinal chemistry, to improve the compounds,” Detweiler said.

“They use chemistry to slightly change the compound, and then we check to identify the changed compounds that work better than the chemicals we found in the screen.”

Detweiler said partnerships between academics and private enterprise are crucial, as many pharmaceutical companies have reduced their own commitment to research and development. Most antibiotics in use today, according to CU, were developed in the 1950s.

For now, despite these recent advancements — chronicled in the journal PLOS Pathogens — Detweiler said it could be five to 10 years before there could be a direct application of her research to the treatment of human disease.

“It’s because the science is just slow, and it’s super important to be careful and the science is maddeningly slow. But if you don’t do it, you don’t get the product — even if it’s 10 years from now,” she said.

“I also feel a strong commitment to serve, essentially the public, That is why anything that could be a useful tool, we will develop. The way I actually view my job. I’m a public servant. I don’t think it’s defined that way. But that’s how I view it.”

Charlie Brennan: 303-473-1327, brennanc@dailycamera.com or twitter.com/chasbrennan

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