Shapeshifting antibiotics fool drug-resistant bacteria
There’s no question that the discovery of antibiotics just under 100 years ago has had a profound impact on the world. However, the rise of drug-resistant bacteria is now painting more of a grim picture, with some studies predicting that it could claim as many as 10 million lives by 2050.
New research out of New York’s Cold Spring Harbor Laboratory (CSHL) suggests that the key may be to beat bacteria at its own game, adapting and changing in real time to topple the pathogens’ defenses.
Using innovative click chemistry, the molecular process that earned scientists Carolyn Bertozzi, Morten Meldal and Barry Sharpless a Nobel Prize in 2022, researchers have created an antibiotic with more than a million configurations to its chemical structure. Drawing surprising inspiration from military tanks and their rotating turrets that can respond fast to threats, the scientists hope this kind of antibiotic could outsmart the kinds of bacteria that existing medicines are increasingly weak against.
“Click chemistry is great,” says John Moses, professor at CSHL. “It gives you certainty and the best chance you’ve got of making complex things.”
The key to the discovery was a molecule called bullvalene, which is a fluxional molecule, meaning its atoms can swap positions. With this molecule at the core, and powerful antibiotic vancomycin as the “warheads” on the outer side, the drug has the ability to “shapeshift” its structure to sneak past the defenses of resistant strains of bacteria.
Importantly, when this new kind of drug was tested in trials on bacteria-infected wax moth larvae, it was more effective than just vancomycin on its own, and the pathogen was unable to develop resistance to it.
And with around three million Americans contracting drug-resistant bacterial or fungal infections each year, and 35,000 dying from these conditions, finding new antibiotics that can outsmart ever-evolving pathogens is critical.
“If we can invent molecules that mean the difference between life and death, that’d be the greatest achievement ever,” said Moses.
The study was published in the journal PNAS.
Source: Cold Spring Harbor Laboratory