Di, Deslouches, and Montelaro develop promising antibiotic molecule for drug-resistant infections


Researchers Develop Promising Antibiotic Molecule for Drug-resistant Lung Infections

CISTIC FIBROSIS NEWS TODAY - A man-made antibiotic able to fight drug-resistant bacteria in the lungs with minimal toxicity to a person’s cells may be a promising approach to eliminate lung infections, such as those caused by resistant Pseudomonas aeruginosa, that trouble people with cystic fibrosis (CF), suggests a study published in the journal Science Advances.

Through serendipity, researchers at the University of Pittsburgh Graduate School of Public Health considerably reduced the toxicity of a potential antibiotic against the most feared drug-resistant bacteria, while also improving its stability in fighting infections.

The new antibiotic -- administered via the windpipe to target lung infections -- proved more effective than its experimental predecessor and traditional last-resort antibiotic therapies in fighting drug-resistant bacteria in laboratory cell cultures and mice. And it did so without notable toxic side-effects, according to findings published today in Science Advances.

"We were so surprised and happy," said lead author Y. Peter Di, Ph.D., M.B.A., associate professor in Pitt Public Health's Department of Environmental and Occupational Health. "At first, we were skeptical and repeated the experiment -- but yes, it was 20 times less toxic toward red blood cells in our lab. And when we saw similar results in mice, we were really excited."

Antimicrobial resistance is listed by the U.S. Centers for Disease Control and Prevention as one of the biggest public health challenges of our time, with someone dying in the U.S. every 15 minutes from an antibiotic-resistant infection. It occurs when bacteria rapidly evolve resistance against antibiotics, making them "superbugs."

The experimental drug that Di's team developed is built from an engineered cationic antimicrobial peptide, or "eCAP," which is a synthetic and more efficient version of naturally occurring antimicrobial peptides that form a first line of defense against infections in humans. Developed by co-authors Berthony Deslouches, M.D., Ph.D., assistant professor in Pitt Public Health's Department of Environmental and Occupational Health, and Ronald Montelaro, Ph.D., professor emeritus in Pitt's Department of Microbiology & Molecular Genetics, eCAPs work by "punching into" bacteria, thereby destroying them. 

“This considerable improvement in lowering toxicity, coupled with the new drug’s strong stability and activity against superbugs, is good evidence that this compound will be well-suited for clinical applications in treating respiratory infections,” added Di.

The team is now exploring D8’s potential as an aerosolized treatment for CF patients burdened with drug-resistant lung infections and for those developing pneumonias associated with mechanical ventilation, as is happening in some people with COVID-19 infections. Overall, “this report underscores the therapeutic potential of D8 in the context of respiratory infections such as those related to CF and ventilator-associated pneumonia, which are often complicated by drug resistance,” the researchers wrote.

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Researchers Develop Promising Antibiotic Molecule for Drug-resistant Lung Infections, by BY Ines Martins, PhD / CYSTIC FIBROSIS, NEWS, May 11, 2020 



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