May 3, 2024

Shape-Shifting Antibiotics – A New Weapon Against Drug-Resistant Superbugs

A couple of years later, Moses learned of a molecule called bullvalene. Bullvalene is a fluxional molecule, meaning its atoms can switch positions. This gives it a changing shape with over a million possible configurations– exactly the fluidity Moses was trying to find.
The chemical structure of the brand-new antibiotic was developed by Moses and synthetically put together by his laboratory. Dr. Thomas Fallon, Moses collaborator at the University of Newcastle, Australia, provided the shape-shifting bullvalene core. Moses says one commenter called the study “most likely the coolest and most intricate natural item derivative paper Ive stumbled upon.” Credit: Moses Lab/Cold Spring Harbor Laboratory
A number of germs, consisting of MRSA, VRSA, and VRE, have established resistance to a powerful antibiotic called vancomycin, utilized to deal with whatever from skin infections to meningitis. Moses thought he could enhance the drugs bacteria-fighting efficiency by combining it with bullvalene.
He relied on click chemistry, a Nobel Prize– winning class of quick, high-yielding chemical reactions that “click” molecules together reliably. This makes the responses more efficient for wide-scale use.
” Click chemistry is terrific,” says Moses, who studied this innovative advancement under two-time Nobel laureate K. Barry Sharpless. “It gives you certainty and the very best opportunity youve got of making complex things.”
Utilizing this method, Moses and his associates developed a brand-new antibiotic with 2 vancomycin “warheads” and a changing bullvalene center.
They discovered the shape-shifting antibiotic considerably more efficient than vancomycin at clearing the deadly infection. Furthermore, the bacteria didnt develop resistance to the new antibiotic.
Researchers can utilize click chemistry with shape-shifting antibiotics to produce a plethora of new drugs, Moses explains. Such weapons versus infection may even be key to our species survival and evolution.
” If we can develop molecules that indicate the distinction in between life and death,” he says, “that d be the best achievement ever.”
Referral: “Shapeshifting bullvalene-linked vancomycin dimers as efficient antibiotics versus multidrug-resistant gram-positive bacteria” by Alessandra Ottonello, Jessica A. Wyllie, Oussama Yahiaoui, Shoujun Sun, Rebecca A. Koelln, Joshua A. Homer, Robert M. Johnson, Ewan Murray, Paul Williams, Jani R. Bolla, Carol V. Robinson, Thomas Fallon, Tatiana P. Soares da Costa and John E. Moses, 3 April 2023, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2208737120.
The study was moneyed by the National Cancer Institute, the Australian Research Council, the National Health and Medical Research Council, the Marsden Fund, the Royal Society University Research Fellowship, Wolfson College, and the Medical Research Council.

Professor John E. Moses has developed a shape-shifting antibiotic using click chemistry, combining vancomycin with bullvalene– a particle with over a million configurations– to produce a more reliable drug that bacteria did not establish resistance to, possibly revolutionizing the battle against drug-resistant infections.
Antibiotic resistance is a major public health threat, ranked as one of the top 10 by the World Health Organization. While antibiotics are vital in dealing with infections, overuse has actually led to the advancement of antibiotic-resistant strains of germs.
Now, Professor John E. Moses of Cold Spring Harbor Laboratory (CSHL) has actually developed a new weapon to fight drug-resistant superbugs– an ingenious antibiotic that has the capability to shape-shift by rearranging its atoms.
Moses came up with the concept of shape-shifting antibiotics while observing tanks in military training workouts. With rotating turrets and active motions, the tanks could react rapidly to possible hazards.

While antibiotics are crucial in dealing with infections, overuse has led to the development of antibiotic-resistant strains of germs. The chemical structure of the new antibiotic was created by Moses and artificially assembled by his lab. The scientists offered the drug to VRE-infected wax moth larvae, which are typically utilized to test prescription antibiotics. They found the shape-shifting antibiotic significantly more effective than vancomycin at clearing the fatal infection. In addition, the germs didnt develop resistance to the new antibiotic.