Study shows how a potential new class of antibiotics works

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Scientists at St. Jude are studying antimicrobial compounds called argyrines. Argyrines have shown some success against a bacterium called Pseudomonas aeruginosa.

The bacterium causes an infection in humans. Antibiotics have become less effective and new drugs are needed. Scientists have shed some light on how argyrines work.

EF-G is a protein that triggers the movement of RNA through the ribosome. The scientists used imaging tools such as cryo-EM and smFRET. The results showed that an argyrine targets EF-G when already bound to the ribosome. This traps EF-G in a certain state, disrupting his movements.

“The slowest steps in biological processes are often the most susceptible to regulation,” said Scott Blanchard, PhD, Structural Biology. “This is true for most of the antibiotics we have reviewed so far and we hope to learn from these observations to inform the development of new therapies.”

Understanding how antibiotics might work will lead to smarter drug development.

Emily Rundlet and Mikael Holm, PhD, of Structural Biology were co-first authors of the study along with authors from the University of Hamburg.

The findings appeared in Proceedings of the National Academy of Sciences.

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