Exploiting C. diff’s Molecular ‘Superpower’

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Credit: CDC

Key points: 

  • A new study shows how two molecular mechanisms work together to make C.diff “extra resistant.”
  • The researchers discovered a novel protein that conveys resistance to a specific class of antibiotics that seems to worsen C.diff infections.

With its affinity for rapidly spreading through healthcare settings, increasing mortality and treatment times, Clostridioides difficile, or C. diff., is one of today’s most problematic superbugs. Trying to understand the bacteria’s underlying molecular mechanisms, a team of researchers from Lund University in Sweden discovered how two molecular mechanisms work together make the bacterium “extra” resistant.

“Using this knowledge, we hope to be able to design even better medicines,” said lead author Vasili Hauryliuk, senior lecturer at Lund University.

The risk of infection with C. diff is known to increase after treatment with an antibiotic called clindamycin, but the reason for this was unknown.

“Instead of the antibiotic saving you, in this case it promotes a secondary bacterial infection,” said Hauryliuk.

In their study, the researchers discovered a novel protein that conveys resistance to the class of antibiotics to which clindamycin belongs. The protein works on the ribosome, which gives bacteria their abilities. That’s what makes the ribosome a primary antibiotic target: if proteins cannot be synthesized, the bacteria will not grow, replicate and cause infection.

Not only does the newly discovered protein kick the antibiotic molecule out of the ribosome, but it also combines with another resistance factor to up its resistance, explain the researchers.

“The second [factor] chemically modifies the ribosome so that the antibiotic molecules bind less tightly to it. The extra-potent resistance is the result of two mechanisms—two factors—that combine. In so doing, [they] give C.diff its ‘superpowers’ against antibiotics,” said Gemma  Atkinson, senior lecturer at Lund University and co-author of the article.

The study also found that certain antibiotics that target the ribosome induce the production of the resistance factor. This may provide clues for designing new antibiotic molecules, since resistance cannot be induced if resistance factors are not synthesized.

 

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