New Compounds Make Old Antibiotics New in the Fight Against Superbugs

With antibiotic-resistant “superbugs” now infecting 2 million people per year and a dearth of new medications in the pipeline to treat them, CU Boulder researchers are taking a novel approach to addressing the looming public health crisis “They’re helping develop new drugs to make old drugs work better.”

Corrie Detweiler, a professor of Molecular, Cellular, and Developmental Biology (MCDB), who recently outlined her discovery in the journal PLOS Pathogens, said:

More than 23,000 people die annually in the United States from bacterial infections that have evolved to resist antibiotics. Thousands more suffer life-threating bouts with once-easily treatable illnesses like strep throat, urinary tract infections, and pneumonia. And some forms of tuberculosis and gonorrhea are now resistant to all available drugs. Detweiler said:

Meanwhile, most antibiotics still in use today were developed in the 1950s, as pharmaceutical companies have scaled back investment in research and development. The last time a new class of antibiotics hit the market was in 1984, according to the Pew Charitable Trust. Detweiler added:

A new way to fight superbugs

To that end, she recently developed a new technique called SAFIRE for screening for new small molecules with anti-microbial properties. Detweiler said:

Rather than pour potential new antibiotics into a test tube teeming with bacteria (as in the past) SAFIRE uses cutting-edge cell imaging techniques to observe what the compounds do to mammalian cells infected with bacteria over 18 hours. The method enables her laboratory to zero in on compounds that keep bacteria from replicating inside the host cell, but don’t harm the host. Detweiler added:

Of 14,400 potential candidates screened, her team has zeroed in on at least three with strong potential. They work not by killing the bacteria itself, but by getting inside it and shutting of cellular machines called “efflux pumps,” which bacteria use to protect themselves from both antibiotic medications and the body’s own immune-boosting proteins.

Corrie Detweiler in her lab at CU Boulder. (Credit: Patrick Campbell/CU Boulder)

Corrie Detweiler in her lab at CU Boulder. (Credit: Patrick Campbell / CU Boulder)

Edward Yu, a professor of pharmacology at Case Western Reserve University who collaborated with Detweiler on the research, said:

Collaborating with industry

Yu notes that because the compounds don’t kill the bacteria themselves, the bacteria don’t learn to resist them — a fact that could give the treatments more staying power than conventional antibiotics have had. The compounds are also potent. In the recently published study, they synergized with the common antibiotics erythromycin and ciproflaxin to reduce replication of Salmonella in infected cells by 10 to 20 fold.

Senior research assistant Amy Crooks, right, works with Corrie Detweiler in the lab. (Image: University of Colorado Boulder)

Senior research assistant Amy Crooks, right, works with Corrie Detweiler in the lab. (Image: University of Colorado Boulder)

In September, the Colorado Office of Economic Development and International Trade awarded Detweiler $125,000, topping off $2 million in National Institutes of Health funding. She’s now collaborating with Boulder-based pharmaceutical start-up Crestone Inc. to help refine the compounds, and hopes to begin testing them in animals soon.

Other co-authors of the PLOS Pathogens paper include: Abigail Reens, MCDB graduate student and first-author; Amy Crooks, senior research assistant; Toni Nagy, postdoctoral research associate; graduate students David Reens, Jessica Podoli, Madeline Edwards; Edward Yu and Chih-Chia Su of Case Western University.

Provided by: University of Colorado Boulder [Note: Materials may be edited for content and length.]

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