New Antibiotic Could be 100 Times More Potent and Has Potential to Save Countless Lives

Back in 2006, a team of chemists began a project to understand how the soil bacterium Streptomyces coelicolor produces the antibiotic methylenomycin A. Little did they know at the time that their investigation would lead to the discovery of an entirely new antibiotic — one that tests have shown is 100 times more effective than the original at defeating drug-resistant superbugs, such as Methicillin-resistant Staphylococcus aureus (MRSA).

“It was really a chance discovery,” co-lead author Professor Greg Challis, in the Department of Chemistry at the University of Warwick, U.K., and Biomedicine Discovery Institute at Monash University, Australia, said in a press release. The team’s work has since been described in the Journal of the American Chemical Society.

“This discovery suggests a new paradigm for antibiotic discovery. By identifying and testing intermediates in the pathways to diverse natural compounds, we may find potent new antibiotics with more resilience to resistance that will aid us in the fight against [antimicrobial resistance],” explained Challis.

Read More: A Deadly Superbug Named Candida Auris Is on the Rise — Who Is at Risk?

Antibiotic Hiding In Plain Sight

Initially, the researchers honed in on the process by which Streptomyces coelicolor produces methylenomycin A, analyzing each stage in detail and methodically deleting genes in the enzymes involved to determine the impact it had on the production of methylenomycin.

Through this process, they discovered various intermediate molecules, which were later tested for antimicrobial activity.

“Methylenomycin A was originally discovered 50 years ago, and while it has been synthesized several times, no one appears to have tested the synthetic intermediates for antimicrobial activity!” said Challis.

During these tests, the intermediate pre-methylenomycin C lactone was found to be two orders of magnitude (or 100 times) more active against Gram-positive bacteria than methylenomycin A. Importantly, it proved to be effective against two bacteria (Staphylococcus aureus and Enterococcus faecium) responsible for MRSA and Vancomycin-resistant Enterococcus (VRE).

Co-lead author Dr. Lona Alkhalaf, Assistant Professor at the University of Warwick, described finding a new antibiotic from a bacterium that has been studied since the 1950s as a “real surprise.”

There are two directions the research can take, Alkhalaf explained. The first is to investigate its potential as an antibiotic and determine whether or not it is a viable drug candidate. The second is to interrogate the activity of pre-methylenomycin C lactone in more detail to see if it is possible to identify potential antibiotics from other intermediates.

“It gives us the impetus to take potentially a whole new research direction where we could start to look more at the intermediates of other antibiotics and [see] if they have this improved activity,” said Alkhalaf.

Christopher Schofield, professor of chemistry at the University of Oxford, U.K., who was not involved in the research, highlighted the significance of the work, explaining molecules such as methylenomycin are important antibiotics that “perhaps have been understudied compared to larger, often easier to study, natural products in recent times.”

“Importantly, the authors show that two biosynthetic intermediates are substantially more active than methylenomycin A itself,” said Schofield.

The Fight Against Antimicrobial Resistance

It was not that long ago that a small cut could be life-threatening, with no effective treatment for blood poisoning, pneumonia, gonorrhea, and many other ailments. The very first true antibiotic was not identified until the 1920s, when Alexander Fleming accidentally (much like Challis and co) discovered penicillin. Even then, it did not become widely available until the 1940s.

Less than a century on, and antimicrobial resistance is one of the most critical public health threats. In 2019, it was held directly responsible for over a million deaths globally, according to the World Health Organization (WHO).

Last month, the WHO released a report warning “too few antibacterials in the pipeline” thanks to a dual crisis of “scarcity and lack of innovation.” While pre-methylenomycin C lactone is far from market-ready — next steps involve pre-clinical testing — the researchers describe it as “a promising starting point for the development of novel antibiotics to combat antimicrobial resistance.”

“What is rewarding and interesting is to see that from systems where we believe we understand everything, we still carry on with making new discoveries, and this is not finished,” said co-lead author Professor Christophe Corre in the Department of Life Sciences at the University of Warwick. “I am sure there is plenty more to understand and discover.”

This article is not offering medical advice and should be used for informational purposes only.

Article Sources

Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:

• This article references information from the recent study published in the Journal of the American Chemical Society: Discovery of Late Intermediates in Methylenomycin Biosynthesis Active against Drug-Resistant Gram-Positive Bacterial Pathogens
• This article references information from the WHO: Antimicrobial resistance
• This article references information from the WHO: WHO releases new reports on new tests and treatments in development for bacterial infections