Transition mutations in the 23S rRNA of erythromycin-resistant isolates of Mycoplasma pneumoniae.
Erythromycin is the drug of choice for treatment of Mycoplasma pneumoniae infections due to its susceptibility to low levels of this antibiotic. After exposure of susceptible strains to erythromycin in vitro and in vivo, mutants resistant to erythromycin and other macrolides were isolated. Their phenotypes have been characterized, but the genetic basis for resistance has never been determined. We isolated two resistant mutants (M129-ER1 and M129-ER2) by growing M. pneumoniae M129 on agar containing different amounts of erythromycin. In broth dilution tests both strains displayed resistance to high levels of several macrolide-lincosamide-streptogramin B (MLS) antibiotics. In binding studies, ribosomes isolated from the resistant strains exhibited significantly lower affinity for [14C]erythromycin than did ribosomes from the M129 parent strain. Sequencing of DNA amplified from the region of the 2S rRNA gene encoding domain V revealed an A-to-G transition in the central loop at position 2063 of M129-ER1 and a similar A-to-G transition at position 2064 in M129-ER2. Transitions at homologous locations in the 23S rRNA from other organisms have been shown to result in resistance to MLS antibiotics. Thus, MLS-like resistance can occur in M. pneumoniae as the result of point mutations in the 23S rRNA gene which reduce the affinity of these antibiotics for the ribosome. Since they involve only single-base changes, development of resistance to erythromycin in vivo by these mechanisms could be relatively frequent event.
Lucier
T S
TS
Department of Pediatrics, University of North Carolina at Chapel Hill 27599, USA.
Heitzman
K
K
Liu
S K
SK
Hu
P C
PC
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D003470:Culture Media; D004352:Drug Resistance, Microbial / Q000235:genetics; D004917:Erythromycin / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009177:Mycoplasma pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000648:ultrastructure; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics*; D012338:RNA, Ribosomal, 23S / Q000235:genetics*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D003470:Culture Media; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D004917:Erythromycin