A model of lariocidin, a molecule previously idenified by the Wright lab that that attacks bacteria in a way that's completely different from other antibiotics. Credit: McMaster University
Researchers in the Wright Laboratory at McMaster University have discovered a new antibiotic that kills some of the world’s most dangerous and drug-resistant bacteria by targeting a previously unknown vulnerability—opening the door to an entirely new class of treatments.
The research marks the fourth major antibiotic discovery from Wright’s lab in just over a year.
In January 2025, Wright and team discovered that limiting zinc availability can make certain drug-resistant bacteria vulnerable to antibiotics they would normally resist or evade. Specifically, they found that when Klebsiella pneumoniae and Pseudomonas aeruginosa are forced to grow in zinc-poor conditions, maintaining resistance to last-resort carbapenem antibiotics becomes more costly for them. This “fitness cost” weakens other defenses, making the bacteria unexpectedly susceptible to azithromycin, a widely used antibiotic that normally does not work well against these gram-negative pathogens.
Then, in March, the McMaster University-based laboratory identified a new class of antibiotics called lariocidin, produced by a type of bacteria that the researchers retrieved from a soil sample collected from a local backyard. The molecule, a lasso peptide, binds directly to a bacterium’s protein synthesis machinery in a completely new way from other antibiotics, inhibiting its ability to grow and survive.
A few months later in October, the Wright Lab discovered a new class of antibacterial proteins that can enter and kill a broad range of bacterial species without needing the specific cell-surface receptors that other antibacterial proteins require. This challenges a long-standing assumption in microbiology that protein-based bacterial toxins are inherently narrow-spectrum and only effective against closely related bacteria.
Now, in this latest research just published in Nature, Wright and team identified a new compound called manikomycin that has shown early effectiveness against priority pathogens including Salmonella, E. coli and Klebsiella.
In the mid-1900s, scientists first discovered that the soil bacterium Streptomyces rimosus produced oxytetracycline, a powerful new drug that would help usher medicine into the antibiotic age. But, S. rimosus and related bacteria have long since been abandoned as a potential source of new antibiotics.
The McMaster University team revisited the bacteria for their research. They used an advanced laboratory technique called fractionation to filter out oxytetracycline and other abundant compounds from the chemical mixtures produced by S. rimosus. This allowed the team to isolate scarcer molecules that had gone unnoticed over the years.
The molecule manikomycin is unique in that it works by blocking the exit site of the ribosome, the protein-producing machinery found inside every bacterial cell. Today, almost all antibiotics target the same handful of vulnerabilities on the ribosome. Thus, bacteria have evolved broad defense strategies against such attacks; however, drugs that attack a different part of the ribosome—such as the exit site—leave them defenseless.
Wright likens the ribosome to a factory assembly line. Finished components, he says, must be moved off of the line before the next piece can advance. Manikomycin blocks the exit lane, causing the entire assembly process to jam and eventually grind to a halt. And, without the ability to produce proteins, bacteria cannot survive.
“Not a single antibiotic prescribed in clinics today does what manikomycin does,” said Wright. “Not azithromycin, not tetracycline, none of them. We’ve not only found a brand-new drug candidate, but we’ve also established a brand-new target in bacteria that could potentially be exploited with other new drugs.”
The research team is now advancing manikomycin toward clinical development. They have already shown that the new antibiotic is not toxic to human cells, and that it works well in a lab-controlled model of infection—both key milestones on the early development pathway.
They are now working on optimizing the drug’s “residency time”—how long it stays active in the body—and have produced 60 different derivatives with plans to push the best one forward.