Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing the cfr Multidrug Resistance Gene

The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribo-somal subunit, including some oxazolidinones, such as linezolid (LZD). The mobile cfr gene was identified in European veteri-nary isolates from the late 1990s, although the earliest report of a clinical cfr-positive strain was the 2005 Colombianmethicillin-resistant Staphylococcus aureus (MRSA) isolate CM05. Here, through retrospective analysis of LZDr clinical strains from a U.S. surveillance program, we identified a cfr-positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5months. Mo-lecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100, spa type t002, andmultilocus sequence type 5 (ST5). In addition to cfr, LZD resistance in 1128105 is partially attributed to the pres-ence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the37-kb conjugative p1128105 cfr-bearing plasmid from 1128105 into S. aureus ATCC 29213 background strains was successful in recapitulating the Cfr antibiogram, as well as resistance to aminoglycosides and trimethoprim. A 7-kb cfr-containing region of p1128105 possessed sequence nearly identical to that found in the Chinese veterinary Proteus vulgaris isolate PV-01 and in U.S. clinical S. aureus isolate 1900, al-though the presence of IS431-like sequences is unique to p1128105. The cfr gene environment in this early clinical cfr-positive isolate has now been identified in Gram-positive and Gram-negative strains of clinical and veterinary origin and has been associ-ated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination