Novel Antibiotic Fights WHO Priority Pathogen VRE
- Chemists at the University of Warwick adn monash University have identified a novel antibiotic, pre-methylenomycin C lactone, demonstrating significant activity against drug-resistant bacterial pathogens, including Methicillin-resistant Staphylococcus...
- The research, published in the Journal of the American Chemical Society, highlights the potential of revisiting established antibiotic production pathways to uncover new therapeutic agents.
- Antimicrobial resistance (AMR) is a critical global health concern.
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New Antibiotic Discovered: pre-methylenomycin C Lactone Shows Promise Against Drug-Resistant Bacteria
Table of Contents
What Happened?
Chemists at the University of Warwick adn monash University have identified a novel antibiotic, pre-methylenomycin C lactone, demonstrating significant activity against drug-resistant bacterial pathogens, including Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE). This finding is particularly noteworthy because the antibiotic was found as an intermediate in the production process of the existing antibiotic, methylenomycin A, and had previously been overlooked.
The research, published in the Journal of the American Chemical Society, highlights the potential of revisiting established antibiotic production pathways to uncover new therapeutic agents. Researchers discovered two previously unknown biosynthetic intermediates, both proving to be more potent than methylenomycin A.
Why This Matters: The Growing Threat of Antimicrobial Resistance
Antimicrobial resistance (AMR) is a critical global health concern. The World health Institution (WHO) recently reported a concerning lack of new antibacterials in development. The “low-hanging fruit” in antibiotic discovery has largely been harvested, and limited financial incentives are hindering further investment in this crucial area.
the emergence of resistant strains like MRSA and VRE poses a significant threat to public health, leading to increased morbidity, mortality, and healthcare costs. New antibiotics are urgently needed to combat these infections effectively.
How Was This Discovered?
The research team, part of the Monash Warwick Alliance Combatting Emerging Superbug Threats Initiative, focused on the biosynthetic pathway of methylenomycin A. Professor Greg Challis explains, “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!”
By strategically deleting biosynthetic genes in Streptomyces coelicolor, the researchers identified pre-methylenomycin C lactone and another intermediate.Testing revealed that pre-methylenomycin C lactone was over 100 times more active against Gram-positive bacteria than methylenomycin A.
The Role of Streptomyces coelicolor
Streptomyces coelicolor is a well-studied model organism for antibiotic production. This discovery underscores the importance of continuing to investigate the metabolic capabilities of these bacteria, even those previously thought to be fully characterized.
Key Findings & Data
| Antibiotic | activity Against S. aureus | Activity Against E. faecalis |
|---|---|---|
| Methylenomycin A | Moderate | Moderate |
| Pre-methylenomycin C Lactone | High (over 100x more active) | High (over 100x more active) |