Avilamycin Induces Structural Changes In Ribosomal Proteins uL16 And CTC That Enhance The Inhibition Of A-Site tRNA Binding

Miri Krupkin 
Massachusetts Institute of Technology,
Department of Biological Engineering
Monday, April 8th, 2019

Albeit many battles have been won in the war on nosocomial pathogens with the discovery of antibiotics, emergence of multi-drug-resistant (MDR) pathogenic strains of Enterococci, Staphylococci and Streptococci gram positive bacteria pose a serious threat on modern medicine. 

The ribosomal antibiotic avilamycin possess inhibitory activity against these gram positive bacteria

We have determined the crystal structures of avilamycin free and in complex with the eubacterial large ribosomal subunit, shedding light on their binding, inhibition, selectivity and resistance modes. These structures reveal novel binding site and mechanism for the orthosomycin family antibiotics, not shared with other antibiotics from other families.

This antibiotic family is extensively metabolized in vivo, thus reducing their ecological toxicity, and placing them at the frontline of drugs with reduced environmental footprint.