Department of Structural Biology, Weizmann Institute, Rehovot 76100, Israel
Resistance to antibiotics is a severe problem in contemporary medicine. Many antibiotics inhibit protein biosynthesis by hampering the ribosome function. Structures of bacterial ribosomes in complex with these antibiotics illuminated common pathways of antibiotics inhibitory action, namely binding to the ribosomal binding sites, but could not illuminate the species-specific diversity in infectious-diseases susceptibility. Recent structural studies on ribosome from a multi-resistant pathogenic bacteria and careful comparisons to previous ribosomes structures revealed novel structural motifs, essential for protein biosynthesis but are not located in the primary ribosomal active sites, hence no mechanism for their modification, which may lead to resistance are currently known, hence if at all, resistance will appear slowly and less efficiently. These findings prompted the design of antibiotics with desired structures that can be optimized in terms of their chemical properties, toxicity, cellular penetration, and species-specificity, thus preserving the microbiome, as well as increasing their bio degradability, thus reducing the ecological hazards caused by the non-digestible components of the current antibiotics’ metabolites.