The global battle against antibiotic-resistant superbugs has become more challenging following a discovery by researchers at McGill University. They identified two enzymes that use a never-before-seen mechanism to confer resistance to aminoglycoside antibiotics, which are broad-spectrum drugs used for severe bacterial infections. This finding opens a new front in the fight against Antimicrobial Resistance (AMR).
Most known resistance enzymes neutralize drugs by mimicking the antibiotic’s target inside the bacterial cell. However, the enzymes AAC(3)-Ia and AAC(3)-XIa deviate from this approach. Using the Canadian Light Source (CLS) for structural analysis, the team determined that the enzymes only bind to the drug when its central ring is twisted into an unusual “pretzel shape,” a conformation the antibiotic assumes only a fraction of the time.
Given this rare binding opportunity, the researchers did not expect the enzymes to be highly effective. The results, however, were surprising: one enzyme, AAC(3)-XIa, performed just as well as traditional, target-mimicking resistance enzymes. Published in Communications Chemistry, this discovery highlights that the mechanisms of resistance are more diverse and complex than previously understood, demanding that researchers take these unconventional enzymes more seriously when identified in bacterial genomes.
Image credit: Communications Chemistry (2025). DOI: 10.1038/s42004-025-01666-0 (Phys.org)
Article can be accessed on: Phys.org
