Researchers Discover “Crafty” Mechanism for Antimicrobial Resistance

Using a combination of computation and physical observation, researchers in Ontario have uncovered a sophisticated and previously unknown mechanism that many bacteria use to resist the rifamycin class of antibiotics.

The resistant bacteria, which occur widely in the environment and in some human pathogens, have developed a protein that can eject the antibiotic from RNA polymerase. Once the rifamycin is dislodged, they use specially adapted proteins to attack and destroy it.

“What we’ve discovered is a brand-new trick up the sleeves of bacteria to evade this class of antibiotics,” says Gerry Wright, who leads the McMaster University-based Global Nexus for Pandemics and Biological Threats. “It’s like a one-two punch. It’s fascinating and it’s so crafty.”

The discovery shows that the mechanisms of antimicrobial resistance (AMR) are more complex and highly evolved than scientists had previously recognized.

Wright and his colleagues are now combing their database of tens of thousands of samples to see if other bacteria use parallel processes and whether they reveal vulnerabilities that can be exploited to create urgently needed new antibiotics.

Wright says the discovery gives him with new respect for nature’s adaptability.  “We’ve been facing this AMR problem for many years,” Wright says. “Every time we think we’ve figured out all the ways bacteria resist antibiotics, along comes something like this, to let us know there are tricks we hadn’t even thought of before.”

AMR is a huge and growing global health concern that should be commanding much more attention and far more research resources, Wright says. Though the effectiveness of penicillin, rifamycin and other established antibiotic treatments is waning quickly, most pharmaceutical companies are not actively developing new antibiotics because the financial return is lower than pursuing drugs patients would use for years, he adds.

“We have to keep reminding people just how tricky these bugs are. We’ve all been focused on COVID these past two and half years, but AMR is still an enormous problem and these bacteria have continued to innovate and diversify their mechanisms of resistance,” he says. “We have to keep working to make sure we really do understand the enemy.”

The findings are detailed in the journal Molecular Cell.