Manikomycin, isolated from Streptomyces rimosus, is the first known antibacterial to hit the E-site of the large ribosomal subunit, a target not used by any current clinical antibiotic.
That mechanism blocked a key protein-synthesis step and showed activity against multiple bacteria, including multidrug-resistant Enterobacteriaceae, while avoiding known resistance defenses tied to older ribosome targets.
McMaster's Wright lab uncovered the compound by filtering out abundant molecules such as oxytetracycline from S. rimosus extracts, revealing scarcer chemicals long overlooked in a bacterium studied for more than 75 years.
The team has already cleared two early hurdles—not toxic to human cells and effective in a lab infection model—and is now optimizing how long the drug stays active in the body.
Sixty derivatives have been produced as the lab pushes the best candidate toward clinical development, reinforcing its claim that even heavily mined actinomycetes can still yield new antibiotics.