A team of scientists from the University of Warwick and Monash University has uncovered a new antibiotic hidden within a bacterium that scientists have studied for over 70 years.
The new compound, called pre-methylenomycin C lactone, was found in Streptomyces coelicolor, a bacterium already known for producing antibiotics. This discovery could become a weapon in the fight against deadly, drug-resistant infections like MRSA and VRE.
Scientists believed they had learned everything about Streptomyces coelicolor, but this new research proved otherwise. By carefully deleting specific genes in the bacterium, the team discovered two new chemical compounds.
One of them turned out to be more than 100 times stronger than existing antibiotics such as methylenomycin A. Even more impressively, bacteria did not develop any resistance to it, a rare occurrence in today’s antibiotic studies.
The research, published in the Journal of the American Chemical Society, was carried out under the Monash Warwick Alliance Combatting Emerging Superbug Threats Initiative. Scientists had been studying this bacterium since the 1950s, yet no one had examined the intermediate stages of how it produces antibiotics. That’s where the secret was hiding all along — inside the molecule’s natural pathway.
Professor Greg Challis, co-lead author of the study from the University of Warwick and Monash University, said,“Methylenomycin A was originally discovered 50 years ago and has been synthesized several times, but no one appears to have tested the synthetic intermediates for antimicrobial activity. By deleting biosynthetic genes, we discovered two previously unknown intermediates, both of which are much more potent antibiotics than methylenomycin A itself.”
The team named one of these intermediates pre-methylenomycin C lactone, a compound that was hiding in plain sight for decades. Once tested, it showed exceptional power against major Gram-positive bacteria, including Staphylococcus aureus and Enterococcus faecium, which cause MRSA and VRE infections.
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Drug-resistant infections have become one of the biggest threats to global health. According to the World Health Organization (WHO), antimicrobial resistance, or AMR, kills over a million people every year.
The WHO has also warned that there are “too few antibacterials in the pipeline,” meaning that very few new antibiotics are being developed. Most easy-to-discover antibiotics have already been found, and because developing new drugs is expensive, many pharmaceutical companies avoid investing in this area.
The new antibiotic not only kills dangerous bacteria but also seems to stop them from becoming resistant. This could give doctors a new and reliable tool to treat infections that no longer respond to existing drugs.
Dr. Lona Alkhalaf, Assistant Professor at the University of Warwick and co-lead author, said, “Remarkably, the bacterium that makes methylenomycin A and pre-methylenomycin C lactone Streptomyces coelicolor is a model antibiotic-producing species that’s been studied extensively since the 1950s. Finding a new antibiotic in such a familiar organism was a real surprise.”
She added that the bacterium may have originally evolved to produce a much stronger antibiotic but gradually shifted toward making a weaker version for other biological purposes.
The research team found that when Enterococcus bacteria were exposed to pre-methylenomycin C lactone, they did not develop resistance even under conditions that usually lead to resistance against vancomycin — one of the last-resort antibiotics used today. This makes the discovery especially hopeful for treating infections that are resistant to vancomycin, such as VRE, which the WHO lists as a “high-priority pathogen.”
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Professor Challis added, “This discovery suggests a new way to look for antibiotics. By studying the intermediate steps in the natural pathways of molecules, we may uncover new compounds that are not only powerful but also harder for bacteria to resist. This could help us greatly in the fight against antimicrobial resistance.”
The next stage in the development of this antibiotic will involve pre-clinical testing to confirm its safety and effectiveness. In another study published in the Journal of Organic Chemistry, a team led by Professor David Lupton at Monash University successfully created a scalable method to synthesize pre-methylenomycin C lactone in the lab.
Professor Lupton explained, “This synthetic route should allow us to create many different versions of the compound so we can study how it works and make it even more effective. With the Centre to Impact AMR at Monash, we now have the platform to move this promising discovery forward.”
Professor Challis put it, “It’s a reminder that innovation often comes from looking again at what we thought we already knew.”
