McMaster researchers discover a new antibiotic — and a new way to kill drug-resistant bacteria

A team led by McMaster University Professor Gerry Wright has identified manikomycin, a new antibiotic that disrupts a previously unknown bacterial vulnerability. The compound targets the ribosome’s exit site, halting protein production in pathogens like *Salmonella*, *E. coli*, and *Klebsiella*—some of the world’s most dangerous drug-resistant bacteria. Unlike existing antibiotics, manikomycin blocks a site never before exploited, leaving bacteria defenseless against this mechanism. Published in *Nature* on June 3, the discovery stems from research revisiting *Streptomyces rimosus*, a soil bacterium long abandoned as a potential antibiotic source. Wright’s lab used fractionation to isolate manikomycin from compounds previously overlooked, including oxytetracycline. The technique revealed hidden molecules, challenging the assumption that *Streptomyces* bacteria had been fully explored. Wright, director of the Michael G. DeGroote Institute of Infectious Disease Research, emphasizes the innovation: no current antibiotic works like manikomycin. By jamming the ribosome’s exit pathway—comparable to blocking a factory’s assembly line—it forces bacteria to shut down protein production, making survival impossible. The team’s prior work has already yielded three other antibiotic candidates in under a year, signaling a new era in drug discovery. Collaborators from the University of Illinois Chicago and the University of Hamburg assisted in the study, which also confirmed manikomycin’s safety for human cells. Postdoctoral fellow Manpreet Kaur, the first author, highlighted fractionation’s potential to uncover more undiscovered antibiotics in well-studied bacteria. Wright’s lab is now advancing manikomycin toward clinical development, aiming to address the global crisis of antibiotic resistance.