title: Inhibition of protein synthesis by streptogramins and related antibiotics.
abstract: The streptogramins and related antibiotics (the lincosamides and macrolides) (MLS) are important inhibitors of bacterial protein synthesis. The key reaction in this process is the formation of a peptide bond between the growing peptide chain (peptidyl-tRNA) linked to the P-site of the 50S ribosome and aminoacyl-tRNA linked to the A site. This reaction is catalysed by the peptidyl transferase catalytic centre of the 50S ribosome. Type A and B streptogramins in particular have been shown to block this reaction through the inhibition of substrate attachment to the A and P sites and inhibition of peptide chain elongation. Synergy between type A and B components results from conformational changes imposed upon the peptidyl transferase centre by type A compounds and by inhibition of both early and late stages of protein synthesis. The conformational change increases ribosomal affinity for type B streptogramins. Microbial resistance to the MLSB antibiotics is largely attributable to mutations of rRNA bases, producing conformational changes in the peptidyl transferase centre. This can result in resistance to a single inhibitor or to a group of antibiotics (MLSB). The activity of type A streptogramin is retained thus explaining the improved inhibitory action of the combined streptogramins against macrolide and lincosamide-resistant strains. However, the development of resistance to the streptogramins may be less of a problem because of the synergic effect of type A and B compounds which has also been demonstrated in strains resistant to MLSB i.e., high level resistance to the combined streptogramins is only likely when type A streptogramin resistance determinants are present along with type B streptogramin resistance determinants.
authors.affiliation: Histology Department, University of Louvain, Medical School, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Cocito
authors.forename: M
authors.initials: M
authors.lastname: Di Giambattista
authors.forename: E
authors.initials: E
authors.lastname: Nyssen
authors.forename: P
authors.initials: P
authors.lastname: Vannuffel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects*; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D010539:Permeability / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012270:Ribosomes / Q000187:drug effects; D014769:Virginiamycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D014769:Virginiamycin; D010458:Peptidyl Transferases