Beneath a patch of soil in Hamilton, Ontario, scientists may have found a long-awaited answer to one of medicine’s most pressing problems.
They found a new molecule named lariocidin—a potential new antibiotic with the power to kill some of the world’s most drug-resistant bacteria. The molecule belongs to a rare class called lasso peptides, and its discovery marks what scientists are calling a major step forward in the decades-long stagnation of antibiotic innovation.
“This is a new molecule with a new mode of action,” said Gerard Wright, senior author of the study and a professor at McMaster University. “It’s a big leap forward for us.”
A potential new antibiotic
For nearly 30 years, no new class of antibiotics has made it to the market. Meanwhile, bacteria have only grown stronger.
Antimicrobial resistance—when pathogens evolve to evade medicines—kills an estimated 4.5 million people each year. The World Health Organization has repeatedly warned that we are teetering on the edge of a post-antibiotic era, where even minor infections could once again become deadly.
“About 4.5 million people die every year due to antibiotic-resistant infections, and it’s only getting worse,” Wright said.
The WHO’s latest analysis of the antibiotic pipeline offers little comfort. Of the 97 antibacterial agents in clinical development as of 2023, only 12 are considered innovative, and just 4 are active against critical pathogens—the ones posing the gravest global threat. And most existing drugs simply aren’t keeping up.
Against this bleak backdrop, lariocidin stands out.
A Lasso-Shaped Antiobitic
Lariocidin belongs to a quirky family of molecules known as lasso peptides. Shaped like microscopic cowboy lassos, these molecules are ribosomally synthesized—stitched together by the cell’s own protein-making machinery—and then folded into a tightly knotted structure. That knot makes them unusually stable, resisting heat, enzymes, and even time.
Scientists have known for years that some lasso peptides can kill bacteria by interfering with key proteins, like RNA polymerase or proteases. But none had ever been shown to attack the ribosome itself—until now.
Using a blend of chemistry, genetics, and structural biology, the team demonstrated that lariocidin binds to a never-before-targeted site on the ribosome. It doesn’t stop protein synthesis by jamming the usual gears. Instead, it stalls the ribosome mid-process and causes it to make catastrophic mistakes.
“Lariocidin binds near the decoding center of the small ribosomal subunit and prevents tRNA from moving through properly,” explained Dr. Yury Polikanov, a structural biologist at the University of Illinois at Chicago and co-lead author of the study. “It also induces ‘miscoding,’ where the wrong amino acids are added into proteins, which can be lethal to bacteria.”
From Dirt to Drug Candidate
The McMaster team discovered lariocidin in an unlikely place—a backyard soil sample. They let the soil’s bacteria grow undisturbed in the lab for an entire year, giving even the slowest-growing species time to emerge. Eventually, they identified a strain of Paenibacillus producing a compound that killed even the most resilient bacteria.
The strain produced a potent antibacterial compound even against colistin-resistant E. coli. Colistin is considered a last-resort antibiotic, so the team knew they were onto something unusual. Further testing confirmed that the active molecule was indeed a lasso peptide, later named lariocidin—or LAR for short.
Lariocidin binds to bacterial protein synthesis machinery in a novel way—shutting down the microbes’ ability to grow. Unlike other antibiotics, it appears to sidestep known mechanisms of resistance.
That could make it especially powerful against strains like Acinetobacter baumannii, a pathogen on the WHO’s list of critical threats. In early tests, lariocidin worked well against this formidable bug—and showed no toxicity to human cells.
“It ticks a lot of the right boxes,” Wright said. “It’s not toxic to human cells, it’s not susceptible to existing mechanisms of antibiotic resistance, and it works well in an animal model of infection.”
Cautious Optimism and a Long Road Ahead
Despite the excitement, researchers are quick to acknowledge the challenges that lie ahead.
“This was the big a-ha! moment,” Wright said. “But now the real hard work begins.”
Because lariocidin is made by bacteria for their own purposes—not ours—producing it in usable quantities poses a major hurdle. The team is now working on methods to modify the molecule and synthesize it more efficiently.
“We’re now working on ripping this molecule apart and putting it back together again to make it a better drug candidate,” Wright said.
This painstaking process is all too familiar in antibiotic research. Even when promising candidates are discovered, they face years—if not decades—of refinement, trials, and regulatory approvals. Since 2017, only 13 new antibiotics have been approved, and just two represent entirely new classes.
Meanwhile, the threat of antimicrobial resistance continues to mount. Without new treatments, a 2024 forecast warned, drug-resistant infections could kill over 39 million people a year by 2050.
An Urgent Global Challenge
The WHO stresses that innovation alone is not enough. Even when new antibiotics are approved, they often fail to reach the people who need them most. In many low- and middle-income countries, access to effective antimicrobials remains limited.
“Antimicrobial resistance is only getting worse yet we’re not developing new trailblazing products fast enough,” said Dr. Yukiko Nakatani, the WHO’s acting Assistant Director-General for Antimicrobial Resistance. “Innovation is badly lacking, yet access is also a serious challenge.”
The lariocidin breakthrough may help reinvigorate a stalled field, drawing attention and resources to antibiotic discovery. But it also underscores the need for better funding, global coordination, and equitable access to life-saving drugs.
For now, the scientists at McMaster are pressing forward, armed with a molecule from the soil and a growing sense of urgency.
“Our old drugs are becoming less and less effective,” Wright said. “We need new options—and we need them fast.”
The study was published last week in Nature.
