Development of novel ribosome-targeting antibiotics (RIBOTARGET)

The ribosome is one of the major targets for antibiotics. Multi-drug resistant pathogens are making our current arsenal of ribosome-targeting antibiotics obsolete, highlighting the need for development of new antimicrobial compounds.

Ongoing project

Here we focus on discovering novel ribosometargeting antibiotics with improved activity and selectivity, with chemical scaffolds that target novel sites on the ribosome and different steps of the translation cycle.

Specifically, we propose to (WP1) develop novel aminoglycoside antibiotics with potent antibacterial activity and improved target selectivity to overcome the toxicity that is associated with this clinically important class of antibiotics; (WP2) develop proline-rich antimicrobial peptides as novel antimicrobial agents by taking advantage of available high resolution ribosome structures and their ease of synthesis and modification; (WP34) utilise high-throughput screening to discover compounds with novel chemical scaffolds that have activity against new cellular targets, such as the (WP3) ribosome rescue systems, and (WP4) stringent response pathways in bacteria.

The consortium aims to characterise the mechanism of action of novel antimicrobial agents as well as their in vivo and in vitro efficacy, in particular against Priority 1 pathogens and Mycobacterium tuberculosis.

 

Project partners

  • Daniel Wilson, University of Hamburg, Germany (Coordinator)
  • C. Axel Innis, Institut Européen de Chimie et Biologie, France
  • Erik Böttger, University of Zurich, Switzerland
  • Vasili Hauryliuk, Umeå University, Sweden
  • Reynald Gillet, Université de Rennes, France
  • Dominik Rejman, The Czech Academy of Sciences, Czech Republic
  • Marco Scocchi, University of Trieste, Italy

 

Publications