Researchers have just identified a powerful new antibiotic, in a significant discovery that was achieved not by breaking new ground, but by revisiting familiar territory.
The compound, premethylenemycin C lactone, was discovered by a team from the University of Warwick in the United Kingdom and Monash University in Australia. While it has never been detected before, it comes from a type of bacteria that scientists have studied for decades.
It could potentially help combat bacteria that have become increasingly resistant to modern treatments; and it is actually a chemical intermediate that is created during the manufacturing process of another antibiotic, methylenemycin A.
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“Surprisingly, the bacteria that produce lactone methylenemycin A and premethylenemycin C – Streptomyces coelicolor – is an antibiotic-producing model species that has been studied extensively since the 1950s,” says chemist Lona Alkhalaf from the University of Warwick.
“Finding a new antibiotic in such a familiar organism was a real surprise.”
In laboratory tests, premethylenemycin C lactone was shown to be 100 times more effective than methylenemycin A against Gram-positive bacteria, which are becoming smarter at outwitting our current antibiotics.
The researchers behind the discovery decided to take a closer look at methylenemycin A by modifying the genes used in the antibiotic’s assembly line, to see what each one did. The antibiotic activity of the resulting compounds, described as biosynthetic intermediates, was then analyzed.
“Methylenemycin A was originally discovered 50 years ago and, although it has been synthesized several times, no one seems to have tested the synthetic intermediates for antimicrobial activity,” says chemist Greg Challis, from the University of Warwick.
The team found that the lactone premethylenemycin C was effective against the bacteria responsible for methicillin resistance. Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus (ERV), two of the infections that are most problematic for existing antibiotics.
What is particularly promising is that enterococcus Bacteria exposed to the lactone premethylenemycin C for 28 days straight did not become resistant to it, suggesting that the compound could remain effective in the long term.
While experts are increasingly concerned about antibiotic resistance (already responsible for millions of deaths each year), the need for new, resistant drugs to fight infections is urgent, as bacteria continue to evolve.
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Next, we need further preclinical and laboratory testing of the premethylenemycin C lactone to fully understand its potential as an antibiotic, both in the mechanisms through which it acts and the pathogens it attacks.
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Researchers also see potential in looking at the intermediates of other antibiotics to see if more compounds like it can be found.
“This discovery suggests a new paradigm for antibiotic discovery,” says Challis.
“By identifying and testing intermediates in the pathways to various natural compounds, we can find new potent antibiotics with more resistance to resistance that will help us in the fight against antimicrobial resistance.”
The research has been published in the Journal of the American Chemical Society.