Open AccessThe Cfr rRNA Methyltransferase Confers Resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A Antibiotics
Author(s) -
Katherine S. Long,
Jacob Poehlsgaard,
Corinna Kehrenberg,
Štefan Schwarz,
Birte Vester
Publication year - 2006
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00131-06
Subject(s) - lincosamides , 23s ribosomal rna , biology , peptidyl transferase , methyltransferase , lincomycin , microbiology and biotechnology , antibiotic resistance , drug resistance , ribosomal rna , genetics , gene , antibiotics , methylation , ribosome , rna
A novel multidrug resistance phenotype mediated by the Cfr rRNA methyltransferase is observed inStaphylococcus aureus andEscherichia coli . Thecfr gene has previously been identified as a phenicol and lincosamide resistance gene on plasmids isolated fromStaphylococcus spp. of animal origin and recently shown to encode a methyltransferase that modifies 23S rRNA at A2503. Antimicrobial susceptibility testing shows thatS. aureus andE. coli strains expressing thecfr gene exhibit elevated MICs to a number of chemically unrelated drugs. The phenotype is named PhLOPSA for resistance to the following drug classes:Ph enicols,L incosamides,O xazolidinones,P leuromutilins, andS treptograminA antibiotics. Each of these five drug classes contains important antimicrobial agents that are currently used in human and/or veterinary medicine. We find that binding of the PhLOPSA drugs, which bind to overlapping sites at the peptidyl transferase center that abut nucleotide A2503, is perturbed upon Cfr-mediated methylation. Decreased drug binding to Cfr-methylated ribosomes has been confirmed by footprinting analysis. No other rRNA methyltransferase is known to confer resistance to five chemically distinct classes of antimicrobials. In addition, the findings described in this study represent the first report of a gene conferring transferable resistance to pleuromutilins and oxazolidinones.