Description:

Title: New insights into translation and ribosome rescue from novel antibiotics.

Description: All bacteria use trans-translation to rescue stalled ribosomes and maintain protein synthesis capacity. We discovered small molecule inhibitors of trans-translation and found that they have potent broad-spectrum antibiotic activity, including the ability to clear a multi-drug resistant Neisseria gonorrhoeae infection from mice after a single oral dose. Using these compounds as chemical biology tools, we identified a new function for ribosomal protein bL27, the protein closest to the catalytic site of the ribosome, and found unexpected interactions between ribosomes and stalled RNA polymerase.