VRSA under a microscope
New shape-shifting antibiotics could fight deadly medically-resistant bacterial infections responsible for more than 1.2 million deaths worldwide every year, according to a new study.
The antibiotic can shape-shift by rearranging its atoms, using new “click” chemistry, a discovery that won the 2022 Nobel Prize.
The drug’s creator, Professor John Moses at Cold Spring Harbor Laboratory (CSHL), New York, found that bullvalene, a fluxional hydrocarbon molecule where atoms can swap positions to form around 1 million combinations, could be used as the molecular center of an antibiotic that would confer such shape-shifting abilities to the drug as well.
Bacterial infections like Vancomycin-Resistant Staphylococcus aureus (VRSA) have developed resistance to the potent antibiotic vancomycin, used to treat diseases from skin infections to meningitis.
“The reengineering of clinically approved antibiotics to evade resistance mechanisms offers a potential near-to short-term solution that takes advantage of established supply chains and clinical success,” Moses and his co-authors wrote in their demonstration paper in PNAS.
Dr. Moses used new click chemistry—where chemical reactions can “click” molecules together reliably—to combine bullvalene with vancomycin.
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Professor Moses created a new antibiotic with two vancomycin “warheads” and a fluctuating bullvalene center, before giving the drug to a VRSA-infected wax moth larvae, a common test dummy for antibiotics.
The shape-shifting antibiotic was significantly more effective than vancomycin at clearing the deadly infection, and the bacteria did not develop resistance to the drug.
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Dr. Moses believes click chemistry can create a host of new shape-shifting drugs “key to our species’ survival.”
“It gives you certainty and the best chance you’ve got of making complex things,” said Moses. “If we can invent molecules that mean the difference between life and death. That’d be the greatest achievement ever.”
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