Discovery of the sophisticated mechanism that bacteria use to resist antibiotics

Researchers have discovered a significant and previously unknown mechanism that many bacteria use to resist antibiotics.

Using a combination of computation and physical observation in the laboratory, the researchers have unraveled a sophisticated process that some commonly occurring bacteria use to save themselves from the rifamycin class of antibiotics, which occur naturally and are also manufactured to treat infectious diseases.

Rifamycins work by binding to RNA polymerase, a protein essential for bacterial life.

The resistant bacteria, which occur widely in the environment and 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," explains researcher Gerry Wright, who leads the McMaster-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.

Now Wright and his colleagues are 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.

Their work is described in a paper published online in the influential journal Molecular Cell.

Wright says the discovery gives him a new respect for nature's adaptability and renews his enthusiasm for finding and exposing other methods bacteria use to ensure their survival.

AMR is a huge and growing global health concern that should be commanding much more attention and far more research resources, Wright says.

Ref:

Gerry Wright et. al, HelR is a helicase-like protein that protects RNA polymerase from rifamycin antibiotics, Molecular Cell, 28-Jul-2022, DOI: 10.1016/j.molcel.2022.06.019