Ketolide resistance in Streptococcus pyogenes correlates with the degree of rRNA dimethylation by Erm

摘要: Summary Macrolide and ketolide antibiotics inhibit protein synthesis on the bacterial ribosome. Resistance to these is conferred by dimethylation at 23S rRNA nucleotide A2058 within ribosomal binding site. This form of resistance encoded erm dimethyltransferase genes, found in many pathogenic bacteria. Clinical isolates Streptococcus pneumoniae with constitutive erm(B) pyogenes erm(A) subtype (TR) are resistant macrolides, but remain susceptible ketolides such as telithromycin. Paradoxically, some strains S. that possess an identical gene clinically well macrolides. Here we explore molecular basis for differences streptococcal using mass spectrometry determine methylation status their rRNAs. We find a correlation between levels A2058-dimethylation resistance, greatest expressing erm(B). In ketolide-sensitive, appreciable proportions monomethylated. Incubation subinhibitory amounts macrolide erythromycin increases proportion dimethylated (in manner comparable inducible strains) reduces susceptibility. The designation ‘constitutive’ should thus be applied reservation most strains. One strain worthy isolate KuoR21, which has lost part regulatory region upstream fully under all growth conditions, this displays highest telithromycin (MIC > 64 µg ml−1).