Structures of MCX-66, MCX-91 and MCX-128 in complex with the wild-type T. thermophilus 70S ribosome. Credit: Nature Chemical Biology (2024). DOI: 10.1038/s41589-024-01685-3
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A new antibiotic that works by disrupting two different cellular targets would make it 100 million times more difficult for bacteria to evolve resistance, according to new research from the University of Illinois Chicago.

For a new paper in Nature Chemical Biology, researchers probed how a class of synthetic drugs called macrolones disrupt bacterial cell function to fight infectious diseases. Their experiments demonstrate that macrolones can work two different ways—either by interfering with protein production or corrupting DNA structure.

Because bacteria would need to implement defenses to both attacks simultaneously, the researchers calculated that drug resistance is nearly impossible.

"The beauty of this antibiotic is that it kills through two different targets in bacteria," said Alexander Mankin, distinguished professor of pharmaceutical sciences at UIC. "If the antibiotic hits both targets at the same concentration, then the bacteria lose their ability to become resistant via acquisition of random mutations in any of the two targets."

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