Inhibition of a protein-protein interaction mediating antibiotic resistance

Bacteria’s ability to evolve and to protect themselves from different antibiotics has become a worldwide problem. It is estimated that in 2050 antimicrobial resistance will be one of the major global problems which will cause 10 million deaths each year [1]. As it remains challenging to find new naturally present antibiotics, the combinational approach using resistance mechanism inhibitors together with the existing antibiotics can help to restore the efficacy of current antibiotics. During translocation the presence of fusidic acid prevents EF-G release from the ribosome, stalling protein synthesis [2,3]. However, one of the most common forms of antibiotic resistance is caused by the expression of the FusB protein [2,3]. The FusB protein binding to EF-G promotes the release of EF-G from the ribosome so the next round of translocation can occur [2,3]. EF-G/GDP release from the ribosome restores the protein synthesis [2,3]. Therefore, the main aim of this project is to find a druggable site for inhibiting the EF-G/FusB complex formation.