At McMaster University, researchers led by Professor Gerry Wright have discovered an antibiotic that attacks bacteria in a way no existing drug does—by blocking the exit site of the ribosome, the cellular machinery responsible for producing proteins. The compound, called manikomycin, emerged from an unlikely source: a soil bacterium called Streptomyces rimosus that scientists have been studying for over 75 years, yet never fully explored.
The discovery matters now more than ever. Antibiotic resistance is a growing global threat as bacteria evolve defenses against the handful of ribosomal vulnerabilities targeted by nearly all drugs in use today. Manikomycin opens a fundamentally different door. It has shown early effectiveness against some of the world's most dangerous pathogens—Salmonella, E. coli, and Klebsiella—organisms that cause serious infections and have developed resistance to conventional treatments.
What makes manikomycin extraordinary is its novelty. "Not a single antibiotic prescribed in clinics today does what manikomycin does," Wright explains. "Not azithromycin, not tetracycline—none of them." Because bacteria have evolved broad defense strategies against the ribosomal targets that existing antibiotics attack, they remain defenseless against this new mechanism. As Wright notes, "over the history of medicine, we've put absolutely no selective pressure on this particular target, so bacteria have no existing resistance mechanisms for manikomycin."
Wright describes the ribosome as a factory assembly line. Proteins are manufactured step by step, with finished components moving off the line so the next piece can advance. Manikomycin blocks the exit lane entirely, jamming the entire process. Without the ability to produce proteins, bacteria cannot survive.
The road to this breakthrough reveals something equally important: the overlooked potential in revisiting old sources. Streptomyces rimosus produced oxytetracycline, a powerful antibiotic discovered more than 75 years ago that helped usher medicine into the antibiotic age. Scientists assumed the microbe had been "mined completely dry"—that every useful compound it could produce had already been found. Wright's team proved otherwise using an advanced technique called fractionation, which filters out abundant compounds from chemical mixtures produced by the bacteria, isolating scarcer molecules that had gone unnoticed for decades.
Postdoctoral fellow Manpreet Kaur, first author on the study published in Nature, emphasizes the broader implications: "There is likely so much still to be discovered through fractionation. Revisiting the extracts of even well-studied bacteria like Streptomyces may lead to similar discoveries in the future."
This discovery is part of a remarkable streak. Manikomycin marks the fourth new antibiotic candidate from Wright's lab in just over a year—evidence of a promising new approach to drug discovery at a time when the world desperately needs fresh solutions. Wright's team is now advancing manikomycin toward clinical development, working with collaborators at the University of Illinois Chicago and the University of Hamburg in Germany. While the path from laboratory discovery to pharmacy shelf is long, this finding suggests that the microbial world still holds secrets worth finding.