Protein synthesis as a target for antibacterial drugs: current status and future opportunities

The discovery and development of clinically useful antibiotic classes, such as the aminoglycosides, macrolides and tetracyclines, have clearly demonstrated that bacterial protein synthesis is a suitable target for drug intervention. New information on the binding of classical protein synthesis inhibitors to ribosomal RNA provides a rational explanation for their selective action against bacteria and also explains why chromosomal point mutations conferring resistance by structural changes at the target site are relatively rare in the majority of bacteria. These principles will be helpful when considering strategies for the screening or design of novel protein synthesis inhibitors that could be developed as new antibiotics. Recent progress in the discovery and development of bacterial protein synthesis inhibitors is illustrated by consideration of the glycylcyclines, ketolides, oxazolidinones and streptogramins.