title: Linezolid-resistant Staphylococcus aureus strain 1128105, the first known clinical isolate possessing the cfr multidrug resistance gene.
abstract: The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid (LZD). The mobile cfr gene was identified in European veterinary isolates from the late 1990s, although the earliest report of a clinical cfr-positive strain was the 2005 Colombian methicillin-resistant Staphylococcus aureus (MRSA) isolate CM05. Here, through retrospective analysis of LZD(r) clinical strains from a U.S. surveillance program, we identified a cfr-positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5 months. Molecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100, spa type t002, and multilocus sequence type 5 (ST5). In addition to cfr, LZD resistance in 1128105 is partially attributed to the presence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the ∼37-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, although 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 associated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination.
authors.affiliation: Trius Therapeutics, Inc., San Diego, California, USA jlocke@cidara.com.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Locke
authors.affiliation: Trius Therapeutics, Inc., San Diego, California, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Zuill
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Caitlyn R
authors.initials: CR
authors.lastname: Scharn
authors.affiliation: Eurofins Global Central Laboratory, Chantilly, Virginia, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Deane
authors.affiliation: Eurofins Global Central Laboratory, Chantilly, Virginia, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
authors.affiliation: Indiana University Health Pathology Laboratory, Indianapolis, Indiana, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Denys
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Richard V
authors.initials: RV
authors.lastname: Goering
authors.affiliation: Trius Therapeutics, Inc., San Diego, California, USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Shaw
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002442:Ceftazidime / Q000627:therapeutic use; D003550:Cystic Fibrosis; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D058885:Multilocus Sequence Typing; D023303:Oxazolidinones / Q000627:therapeutic use*; D010957:Plasmids / Q000235:genetics; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014031:Tobramycin / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C539943:CFR protein, Staphylococcus aureus; D004269:DNA, Bacterial; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D002442:Ceftazidime; D000069349:Linezolid; D014031:Tobramycin