Scientists at St. Jude are studying antimicrobial compounds called argyrins. Argyrins have shown some success against a bacterium called Pseudomonas aeruginosa.
The bacterium causes infection in humans. Antibiotics have become less effective and new drugs are needed. The scientists shed light on how argyrins work.
EF-G is a protein that kickstarts the movement of RNA through the ribosome. The scientists used imaging tools such as cryo-EM and smFRET. Results showed that an argyrin targets EF-G when it is already bound to the ribosome. This traps EF-G in a certain state, disrupting its movements.
“The slowest steps of biological processes are often the most sensitive to regulation,” said Scott Blanchard, PhD, Structural Biology. “This holds true for most antibiotics we have examined thus far and we are hoping to learn from these observations to inform the development of new therapeutics.”
Understanding how potential antibiotics function will lead to smarter drug development.
Emily Rundlet and Mikael Holm, PhD, of Structural Biology were co-first authors of the study with authors at University of Hamburg.
The findings appeared in Proceedings of the National Academy of Science.