antibiotics The jars contain various cell wall precursors that the Bonn researchers isolated for analysis, including the target structures of clovibactin.
Photo ©Gregor Hübl/University of Bonn
New antibiotic
sourced from ‘microbial dark matter’
A powerful new antibiotic, dubbed ‘clovibactin’ and isolated from bacteria that could not be studied before, seems capable of combating harmful bacteria and even multi-resistant ‘superbugs’ in an unusual manner, making it more difficult for the bacteria to develop any resistance against it.
A
be grown in laboratories previously, and therefore
They utilised solid-state nuclear magnetic resonance
not be mined for novel antibiotics.)
(NMR) spectroscopy, which allows clovibactin’s
Using their device, called iCHip, the US researchers discovered clovibactin in a bacterium
mechanism to be studied under similar conditions as in bacteria.
isolated from a sandy soil from North Carolina: E.
“Clovibactin wraps around the pyrophosphate
terrae ssp. Carolina. Since clovibactin was isolated
like a tight glove, like a cage that encloses its
from bacteria that could not be grown before,
target,” Weingarth said. Furthermore, clovibactin
pathogenic bacteria have not seen such an antibiotic
only binds to the pyrophosphate that is common
before and have had no time to develop resistance.
to cell wall precursors, ignoring that variable
In a study published in the journal Cell,
sugar-peptide part of the targets.
NovoBiotic Pharmaceuticals showed that
“As clovibactin only binds to the immutable,
clovibactin successfully attacks a broad spectrum
conserved part of its targets, bacteria will have
of bacterial pathogens. It was also successfully
a much harder time developing any resistance
used to treat mice infected with the superbug
against it,” Weingarth said. “In fact, we did
Staphylococcus aureus.
not observe any resistance to clovibactin in our
ntimicrobial resistance is a major
Clovibactin appears to have an unusual killing
problem for human health, and researchers
mechanism. It targets not just one, but three
studies.” Furthermore, upon binding the target
worldwide are looking for new solutions. However,
different precursor molecules that are all essential
molecules, clovibactin self-assembles into large
the discovery of new antibiotics is a challenge: few
for the construction of the cell wall, an envelope-
fibrils on the surface of bacterial membranes.
new antibiotics have been introduced over the last
like structure that surrounds bacteria. This was
These fibrils are stable for a long time and
decades, and they often resemble older, already
discovered by the group of study co-author Professor
thereby ensure that the target molecules remain
known antibiotics.
Tanja Schneider, from the University of Bonn.
sequestered for as long as necessary to kill bacteria.
Clovibactin was discovered by NovoBiotic
“The multi-target attack mechanism of
“Since these fibrils only form on bacterial
Pharmaceuticals, a small US-based early-stage
clovibactin blocks bacterial cell wall synthesis
membranes and not on human membranes, they
company, and microbiologist Professor Kim Lewis
simultaneously at different positions,” Schneider said.
are presumably also the reason why clovibactin
from Northeastern University in Boston. They
“This improves the drug’s activity and substantially
selectively damages bacterial cells but is not toxic
had previously developed a device that enables
increases its robustness to resistance development.”
to human cells,” Weingarth said. “Clovibactin
researchers to grow microbial dark matter, which
How exactly clovibactin blocks the synthesis
hence has potential for the design of improved
are so-called unculturable bacteria. (Interestingly,
of the bacterial cell wall was unravelled by a team
therapeutics that kill bacterial pathogens without
99% of all bacteria are ‘unculturable’ and could not
led by Dr Markus Weingarth at Utrecht University.
resistance development.”
24 | LAB+LIFE SCIENTIST - Oct/Nov 2023
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