Discovery shows that antimicrobial resistance is more developed than previously thought

Scientists have discovered an important and previously unknown mechanism that many bacteria use to resist antibiotics.

Using a combination of calculations and physical observations in the laboratory, the researchers revealed a sophisticated process that some common bacteria use to protect themselves against 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 to bacterial life.

Resistant bacteria, widely present in the environment and in some human pathogens, have evolved a protein capable of knocking out the antibiotic from RNA polymerase. Once the rifamycin is released, they use specially adapted proteins to attack and destroy it.

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

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 scouring their database of tens of thousands of samples to see if other bacteria use parallel processes and if they reveal any vulnerabilities that can be exploited to create much-needed new antibiotics.

Their work is described in an article published online today in the influential journal molecular cell. Wright’s co-authors are Matthew Surette, Kalinka Koteva and Nicholas Waglechner.

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

“We’ve had this RAM problem for many years,” says Wright. “Every time we think we’ve discovered all the ways bacteria resist antibiotics, something like this happens to tell us there are tricks we haven’t even thought of before.”

AMR is a huge and growing global health problem that should get a lot more attention and a lot more research resources, says Wright.

Although the effectiveness of penicillin, rifamycin and other established antibiotic treatments is rapidly declining, most pharmaceutical companies are not actively developing new antibiotics, he says.

Wright explains that drug discovery and development is extremely expensive, and the economic return on investment in antibiotics would be low because they do not generate as much revenue as prescription drugs that patients use for years.

The threat to public health from AMR is simply too great to ignore and requires collaboration between governments, universities and manufacturers, says Wright.

“We need to keep reminding people how delicate these bugs are. We’ve all been focused on COVID for the last two and a half years, but AMR remains a huge problem and these bacteria have continued to innovate and diversify their resistance mechanisms,” he says. “We have to keep working to make sure we really understand the enemy.”

Source of the story:

Materials provided by McMaster University. Originally written by Wade Hemsworth. Note: Content can be edited for style and length.

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