Researchers have found a powerful new antibiotic candidate, lariocidin, that could combat drug-resistant bacteria and transform the fight against antimicrobial resistance.
It has been nearly thirty years since a new class of antibiotics reached the market, but that could soon change. Researchers at McMaster University have made a breakthrough that could help turn the tide against drug-resistant bacteria.
Led by scientist Gerry Wright, the team has discovered a powerful new molecule called lariocidin. This promising candidate shows the ability to fight some of the toughest, most drug-resistant bacteria known to science. Their groundbreaking findings were published in the journal Nature.
The rise of bacteria that can resist existing medicines, a phenomenon known as antimicrobial resistance (AMR), has become a major threat to global health. According to the World Health Organization, AMR is now one of the top challenges facing public health worldwide. The urgent need for new antimicrobial medicines has never been greater, and lariocidin offers a fresh hope for the future.
“Our old drugs are becoming less and less effective as bacteria become more and more resistant to them,” explains Gerry Wright, a professor in McMaster’s Department of Biochemistry and Biomedical Sciences and a researcher at the university’s Michael G. DeGroote Institute for Infectious Disease Research. “About 4.5 million people die every year due to antibiotic-resistant infections, and it’s only getting worse.”
Wright and his team found that the new molecule, a lasso peptide, holds great promise as an early drug lead because it attacks bacteria in a way that’s different from other antibiotics. Lariocidin binds directly to a bacterium’s protein synthesis machinery in a completely new way, inhibiting its ability to grow and survive.
“This is a new molecule with a new mode of action,” Wright says. “It’s a big leap forward for us.”
From Soil to Breakthrough
Lariocidin is produced by a type of bacteria called Paenibacillus, which the researchers retrieved from a soil sample collected from a Hamilton backyard.
The research team allowed the soil bacteria to grow in the lab for approximately one year — a method that helped reveal even the slow-growing species that could have otherwise been missed. One of these bacteria, Paenibacillus, was producing a new substance that had strong activity against other bacteria, including those typically resistant to antibiotics.
“When we figured out how this new molecule kills other bacteria, it was a breakthrough moment,” says Manoj Jangra, a postdoctoral fellow in Wright’s lab.
In addition to its unique mode of action and its activity against otherwise drug-resistant bacteria, the researchers are optimistic about lariocidin because it ticks a lot of the right
boxes: it’s not toxic to human cells, it’s not susceptible to existing mechanisms of antibiotic resistance, and it also works well in an animal model of infection.
Wright and his team are now laser-focused on finding ways to modify the molecule and produce it in quantities large enough to allow for clinical development. Wright says because this new molecule is produced by bacteria — and “bacteria aren’t interested in making new drugs for us” — much time and resources are needed before lariocidin is ready for market.
“The initial discovery — the big a-ha! moment — was astounding for us, but now the real hard work begins,” Wright says. “We’re now working on ripping this molecule apart and putting it back together again to make it a better drug candidate.”
Reference: “A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome” by Manoj Jangra, Dmitrii Y. Travin, Elena V. Aleksandrova, Manpreet Kaur, Lena Darwish, Kalinka Koteva, Dorota Klepacki, Wenliang Wang, Maya Tiffany, Akosiererem Sokaribo, Brian K. Coombes, Nora Vázquez-Laslop, Yury S. Polikanov, Alexander S. Mankin and Gerard D. Wright, 26 March 2025, Nature.
DOI: 10.1038/s41586-025-08723-7
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