Pneumococcal resistance to macrolides, lincosamides, ketolides, and streptogramin B agents: molecular mechanisms and resistance phenotypes.
The macrolides, lincosamides, ketolides, and streptogramin B agents (the MLKS(B) antimicrobial agents) have related chemical structures and share similar molecular targets on the 50S ribosomal subunit of Streptococcus pneumoniae. Mutations in rRNA or ribosomal proteins generate a variety of resistance phenotypes. The M phenotype of S. pneumoniae, which predominates in North America, affords low-level resistance to macrolides only (excluding macrolides with 16-member rings) by means of an efflux pump encoded by the mefA gene. The MLS(B) phenotype, which predominates in Europe, affords high-level resistance to macrolides, lincosamides, and streptogramin B agents and arises, in most cases, from dimethylation of adenine 2058 in the 23S rRNA of the 50S ribosomal subunit. Other, less common, phenotypes arise from other 23S rRNA modifications (ML and K phenotypes) or from amino acid substitution (MS(B) phenotype) or insertion (MKS(B) phenotype) into the 50S subunit ribosomal protein L4. In all cases, the decrease in susceptibility to ketolides (for example, telithromycin) is less than the decrease in susceptibility for other MLKS(B) agents.
Edelstein
Paul H
PH
Dept. of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, 19104-4283, USA. phe@mail.med.upenn.edu
D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D048628:Ketolides; D055231:Lincosamides; D018942:Macrolides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D025381:Streptogramin B / Q000494:pharmacology
D001426:Bacterial Proteins; D048628:Ketolides; D055231:Lincosamides; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D012335:RNA, Ribosomal; D012338:RNA, Ribosomal, 23S; D025381:Streptogramin B; C106791:telithromycin