Discovery of New Antibiotic Compound
Researchers have made an intriguing discovery: the first member of a new class of antibiotics, even though they didn’t set out to find new drugs initially.
This fresh antibiotic compound exhibits strong effectiveness against resistant infections, notably methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium, both of which are known for causing hard-to-treat infections in hospitals.
The novel molecule, named pre-methylenomycin C lactone, was unveiled on October 27 and can be regarded as the first in its class, according to chemists Lona Alkhalaf and Greg Challis, who led the study. They shared insights about their findings via email with Live Science.
Interestingly, the research team wasn’t originally on a quest for new antibiotics. Their focus was on understanding how a previously known antibiotic, methylenomycin A, is produced by a soil-based bacterium called Streptomyces coelicolor.
Plants and microorganisms generate a variety of complex secondary metabolites, many of which hold medicinal value for humans. Grasping how these substances are created and how they interact with human cells can pave the way for new drug development.
The key to producing these compounds lies in specific gene collections known as “biosynthetic gene clusters.” By removing specific genes from these clusters, Alkhalaf and Challis could selectively eliminate enzymes involved in making methylenomycin A, allowing them to halt the synthesis process at strategic points for further investigation. This method led to the identification of previously unseen intermediate compounds.
Through this detailed approach, the researchers isolated two novel molecules, pre-methylenomycin C and pre-methylenomycin C lactone. After employing various techniques to thoroughly characterize their structures, they examined the biological activity of these compounds against several bacterial strains.
Pre-methylenomycin C lactone showed significant promise. According to Challis and Alkhalaf, it is particularly effective against a wide range of Gram-positive bacteria, including MRSA and a drug-resistant strain of Enterococcus faecium. They noted that it is “100 times more effective” at destroying drug-resistant bacteria compared to the original antibiotic.
What’s perhaps even more important is that this new compound doesn’t seem to provoke antibiotic resistance in the bacteria it targets.
Chronic exposure to antibiotics often leads to the development of resistance in bacteria, complicating future treatments. In a 28-day experiment involving E. faecium, the bacteria were subjected to increasing amounts of pre-methylenomycin C lactone. Surprisingly, the researchers didn’t see any rise in the minimum inhibitory concentration during that time, suggesting that the antibiotic maintained its potency without fostering resistance.
Going forward, the team plans to broaden their research to include more bacterial strains and to observe how the drugs perform over an extended period. Alkhalaf and Challis aim to show the full potential of their new discovery.
Stephen Cochrane, a medicinal chemist at Queen’s University Belfast, praised the study and remarked on the importance of pursuing novel activities with newly isolated molecules. However, he emphasized the substantial gap that exists between identifying a compound with antibacterial properties and developing it into a usable drug.
Cochrane pointed out the hurdles, such as ensuring the compound lasts long enough in the human body, is safe for use, and doesn’t readily lead to resistance.
For Alkhalaf and Challis, the immediate next step is to collaborate with David Lupton, a synthetic chemist at Monash University in Australia, to devise a method for chemical synthesis of pre-methylenomycin C lactone. This approach would involve creating the molecule from scratch, rather than depending on natural microbial production. The goal is to generate larger quantities for further study, aiming to better understand how the molecule operates and its impact on human cells.
They expressed interest in identifying the biological targets of the compound within susceptible bacteria and exploring how varying the compound’s structure might influence its binding and biological activity. This knowledge could be crucial for designing even more effective antibiotic compounds.
