MOST POTENT ANTIBIOTIC SO FAR, UNCOVERED
A team of chemists stumbled on a game-changing antibiotic hiding in a place no one expected: inside a familiar bacterium that scientists have studied for decades. This molecule is 100 times stronger than existing antibiotics, shows no signs of resistance so far, and could finally turn the tide against superbugs like MRSA and VRE.
Old Bacteria, New Tricks
The breakthrough, led by researchers from the University of Warwick and Monash University, was made possible through creative thinking. Instead of searching for exotic microbes, the scientists looked more closely at Streptomyces coelicolor, a “model” bacterium famous for producing antibiotics and a familiar presence in labs since the 1950s. Buried in its regular antibiotic production line, they found a chemical intermediate named pre-methylenomycin C lactone. Nobody had ever tested it for antibiotic properties before.
And that’s where things got interesting.
According to Professor Greg Challis, who co-led the project, “Methylenomycin A was discovered fifty years ago, and even though people have been making it in the lab ever since, nobody stopped to check what all the precursor chemicals could do. When we deleted some of the genes responsible for making the final product, suddenly these two powerful new antibiotics popped out—and one of them left methylenomycin A in the dust.”
Outsmarting Superbugs
The newly identified intermediate, pre-methylenomycin C lactone, not only surpassed its parent molecule but also. In lab tests, it was more than 100 times more potent against a range of dangerous Gram-positive bacteria, including those responsible for MRSA and VRE—superbugs that are resistant to most available drugs.
Finding a blockbuster antibiotic tucked away in such a well-studied bacterium was, as Dr. Lona Alkhalaf of Warwick put it, “a real surprise.” Evolution, it turns out, might have pushed S. coelicolor to swap out the potent drug for a milder one, perhaps to serve a different purpose in its natural world.
Most exciting: bacteria exposed to the new molecule didn’t manage to develop resistance, even under conditions where they quickly adapt to vancomycin—a last-resort antibiotic in many hospitals. That gives researchers hope that pre-methylenomycin C lactone may continue to work even as other drugs fail.
A Fresh Playbook for Antibiotic Discovery
The World Health Organization has sounded the alarm on antimicrobial resistance, warning of a shortage of new drugs in development and a lack of financial incentives for pharmaceutical companies. This discovery points to an alternative strategy: instead of just hunting for new organisms, dig deeper into familiar ones and test all the “in between” chemicals they produce.
With pre-clinical trials next, the Warwick-Monash team has already developed a scalable synthesis pathway, making it easy to produce sufficient quantities for additional research and even tweak the molecule to enhance its effectiveness.
As Professor David Lupton of Monash notes, “Having a practical synthesis means we can not only study this antibiotic’s structure and mechanism, but also explore analogues that might be even better. With support from the Centre to Impact AMR at Monash, we have a lot of momentum to move forward.”
The Bigger Picture
This is one of those rare wins in the long, tough battle against superbugs. If all goes well, pre-methylenomycin C lactone—or an improved version of it—could save lives at a time when resistance is claiming the lives of over a million people each year. And perhaps more importantly, it’s proof that scientific curiosity and doggedness can still deliver surprises, even from the most familiar sources.
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