Scientists have isolated a possible new antibiotic from a strain of bacterium found in sandy soil from North Carolina.
The way it works could make pathogens less likely to develop drug resistance.
The potent substance, called clovibactin, has only recently been discovered in the labs of the pharmaceutical start-up NovoBiotic. If it eventually proves safe, it will take about a decade to develop into something health practitioners can actually use.
Nevertheless, researchers behind the discovery are excited.
“I think this is the end of the road in the evolution towards resistance avoidance by antibiotics,” states Northeastern University microbiologist Kim Lewis.
That’s amazing to hear in the midst of a growing antimicrobial resistance crisis, which was the third leading global cause of death in 2019 and is expected to contribute to ten million deaths per year by 2050.
But there’s reason to remain cautious in our optimism.
“We’re at step one,” notes Lewis. But “the most important thing about clovibactin, apart from its promise as a drug lead, is that it expands our understanding of antibiotics and what is possible.”
Developing new antibiotics has proven challenging in part because 99 percent of bacteria species won’t cooperatively grow in the lab.
Using a technique developed in previous work, Lewis and team took an isolate of sandy soil and extended its incubation period to see if this would encourage any new types of bacteria to grow in the lab. After three months the new species Eleftheria terrae carolina emerged.
From this the team isolated clovibactin.
“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” explains Utrecht University chemist Markus Weingarth.
Clovibactin parks itself on bacteria’s innard-encasing envelope. Here, it collects and binds stringy fibrils of peptidoglycan molecules, which bacteria use to build the cell membrane on which it sits. The bacteria then destroy their own membrane in a futile attempt to eliminate this wormy hitchhiker.
Time series of the growing wormy molecule (top) and details of its creation below. (Shukla et al. Cell, 2023)
“The most exciting thing is that it is unique and binds an extremely simple target (phosphate molecules) that cannot change,” explains Lewis.
“This is the first discovery of a compound that binds a simple immutable target.”
Because the phosphate part of the cell wall building molecule is crucial for the molecule to perform its function, the bacteria can’t change the structure without consequences as they successfully do with other antibiotic target molecules. But this is just one way bacteria develop antibiotic resistance, so there are no guarantees.
Clovibactin has already cleared MRSA infections in mice and proved non-toxic to cultured human lab cells. The researchers did not detect the slightest hint of resistance during these experiments.
While there’s still much to do, Shukla and colleague’s research demonstrates the potential for at least long-effective antibiotics is very real.
This research was published in Cell.
