Poster abstracts
Poster number 16 submitted by Chih-Wei Chen
Synergistic properties of ribosome-targeting macrolides and hygromycin A
Chih Wei Chen (University of Illinois at Chicago), Yury Polikanov (University of Illinois at Chicago)
Abstract:
Antibiotic resistance is one of the fastest-growing and significant issue in healthcare. Bacteria can employ various methods to circumvent the effects of antibiotics that bind to the ribosome, the main target for antibacterial drugs. One approach to overcome antibiotic resistance is utilizing synergistic combinations of antibiotics. Currently, there are limited pairings of ribosome-targeting antibiotics that exhibit synergy. In this work, we discovered a novel combination of antibiotics (hygromycin A/macrolide) that display cooperativity in ribosome binding as well as antimicrobial function. We obtained crystal structures of hygromycin A bound simultaneously with one of three different macrolides (Erythromycin, azithromycin and telithromycin) in complex with Thermus thermophilus 70S ribosome at a high resolution (2.45 to 2.6Å). Our structures allows us to elucidate the mechanism of action of the observed binding and antimicrobial cooperativity. Through our study, we provide a new direction for the development and discovery of synergistic antibiotic tandems.
Keywords: Ribosome, Macrolides, Hygromycin A