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POWERFUL NEW ANTIBIOTIC THAT CAN KILL SUPERBUGS DISCOVERED IN SOIL
BACTERIA  
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Miryam Naddaf
October 31, 2025
Nature [[link removed]]

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_ Surprise discovery could pave the way for new treatments against
drug-resistant infections. _

NEWS 31 October 2025 Powerful new antibiotic that can kill superbugs
discovered in soil bacteria Surprise discovery could pave the way for
new treatments against drug-resistant infections. By Miryam Naddaf
Twitter Facebook Email Close up of a colony of St, Dr Jeremy
Burgess/Science Photo Library

 

By studying the process through which a soil bacterium naturally
produces a well-known drug, scientists have discovered a powerful
antibiotic that could help to fight drug-resistant infections.

In experiments described in the _Journal of the American Chemical
Society_ on Monday1
[[link removed]], the team
studied the multi-step pathway that the bacterium _Streptomyces
coelicolor_ uses to make the antibiotic methylenomycin A, which was
first identified in 19652
[[link removed]],3
[[link removed]]. They
discovered an intermediate compound — called premethylenomycin C
lactone — whose antimicrobial activity was 100 times stronger than
that of the final product. Tiny doses of it killed strains of bacteria
known to cause hard-to-treat infections.

The discovery was a ‘surprise’, says study co-author Gregory
Challis, a chemical biologist at the University of Warwick in
Coventry, UK. “As humans, we anticipate that evolution perfects the
end product, and so you’d expect the final molecule to be the best
antibiotic, and the intermediates to be less potent,” he says. But
the finding “is a great example of what a ‘blind watchmaker’
evolution is. And it’s a good way of exemplifying it in a very
molecular way,” adds Challis.

Antimicrobial resistance
[[link removed]] is a growing
threat, projected to cause 39 million deaths worldwide over the next
25 years. Researchers say that the discovery of a potent antimicrobial
compound might lead to fresh drugs to tackle resistance.

The work underscores “the potential of such studies to identify new
bioactive chemical scaffolds from ‘old’ pathways”, says Gerard
Wright, a biochemist at McMaster University in Hamilton, Canada.

ACCIDENTAL DISCOVERY

In 2006, Challis and his colleagues began studying the molecular
pathway through which _Streptomyces coelicolor_ produces
methylenomycin A. To do this, they deleted the genes encoding enzymes
involved in each step, one by one. Their work built on earlier efforts
in 2002 to sequence the bacterium’s genome4
[[link removed]].

By 2010, the team had mapped the mechanism that the bacterium used to
make methylenomycin A and identified several intermediate molecules
that it produced along the way.

“We were just doing very fundamental blue-sky research,” says
Challis. “We discovered these intermediates, and we left them for a
while because we didn’t quite know what to do with them.”

It was several years later — around 2017 — that a PhD student at
Challis’s laboratory tested these intermediate molecules for
antimicrobial activity.

These tests revealed that two molecules, including premethylenomycin C
lactone, were much more effective than methylenomycin A at targeting
seven strains of Gram-positive bacteria, including _Staphylococcus
aureus_, which infects skin, blood and internal organs, and
_Enterococcus faecium_, which can cause deadly bloodstream and urinary
infections.

The lowest concentration of premethylenomycin C lactone needed to kill
drug-resistant strains of _Staphylococcus aureus_ was just 1 microgram
per millilitre, compared with 256 micrograms per millilitre of
methylenomycin A. The compound could also kill bacteria at much
smaller doses than those needed for vancomycin, a ‘last line’
antibiotic used to treat infections caused by two _Enterococcus
faecium_ strains, to be effective.

The team then tested whether_ E. faecium_ could develop resistance to
the newly discovered antibiotic. They treated bacteria with increasing
concentrations of premethylenomycin C lactone for 28 days and compared
the results with those of vancomycin.

Vancomycin-treated bacteria mutated and developed resistance — after
28 days, eight times higher doses of the drug were needed to stop
their growth. But the amount of premethylenomycin C lactone that was
effective did not change over the course of the experiment, suggesting
that _E. faecium_ does not easily develop resistance to the new
molecule.

The work “is a lovely example of how basic research on a chemically
interesting antibiotic can have unexpected benefit”, says
Christopher Schofield, a chemist who studies antibacterial resistance
at the University of Oxford, UK.

FUTURE DIRECTIONS

Earlier this year, another research group collaborated with
Challis’s team to develop a cost-effective way to synthesize the
antibiotic using commercial materials5
[[link removed]], which
might help to produce it at scale.

But the researchers first plan to explore how exactly the molecule
works against bacteria. “We still don’t really know where it
targets. We think it targets the cell wall in some way,” says study
co-author Lona Alkhalaf, a chemical biologist at the University of
Warwick.

Challis adds that further research is needed to test the molecule’s
toxicity in mammalian cells. Understanding the mechanism of action and
toxicity could allow researchers to engineer analogues “where we
retain the activity against the target in the bacteria, but we
engineer out any other activities that might be causing toxicity in
humans”, he says.

_doi: [link removed]

REFERENCES

*
Corre, C. _et al._ _J. Am. Chem. Soc_.
[link removed] (2025).

ARTICLE [[link removed]] GOOGLE SCHOLAR
[[link removed].] 

*
Wallhausser, K. H., Nesemann, G., Prave, P., & Steigler, A.
_Antimicrob. Agents Chemother._ 5, 734–736 (1965).

PUBMED
[[link removed]] GOOGLE
SCHOLAR
[[link removed].] 

*
Huber, G. _et al._ _Antimicrob. Agents Chemother._ 5, 737–742
(1965).

PUBMED
[[link removed]] GOOGLE
SCHOLAR
[[link removed].] 

*
Bentley, S. D. _et al._ _Nature_ 417, 141–147 (2002).

ARTICLE [[link removed]] PUBMED
[[link removed]] GOOGLE
SCHOLAR
[[link removed].] 

*
Wright, A. _et al._ _J. Org. Chem._ 90, 11230–11236 (2025).

ARTICLE [[link removed]] PUBMED
[[link removed]] GOOGLE
SCHOLAR
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‘TIS THE SEASON
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STEIER, DRPH, AMY GRAGNOLATI, PHARMD, AND ELANA PEARL BENJOSEPH, MD,
MPHUNBIASED SCIENCENew vaccines and antibodies mean fewer hospital
stays and more holiday celebrationsOctober 29, 2025

 

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