title: A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin.
abstract: OBJECTIVE
  The oxazolidinone-resistant Enterococcus faecalis E349 from a human patient tested negative for the cfr gene and 23S rRNA mutations. Here we report the identification of a novel oxazolidinone resistance gene, optrA, and a first investigation of the extent to which this gene was present in E. faecalis and Enterococcus faecium from humans and food-producing animals.
  
  
  METHODS
  The resistance gene optrA was identified by whole-plasmid sequencing and subsequent cloning and expression in a susceptible Enterococcus host. Transformation and conjugation assays served to investigate the transferability of optrA. All optrA-positive E. faecalis and E. faecium isolates of human and animal origin were analysed for their MICs and their genotype, as well as the location of optrA.
  
  
  RESULTS
  The novel plasmid-borne ABC transporter gene optrA from E. faecalis E349 conferred combined resistance or elevated MICs (when no clinical breakpoints were available) to oxazolidinones (linezolid and tedizolid) and phenicols (chloramphenicol and florfenicol). The corresponding conjugative plasmid pE349, on which optrA was located, had a size of 36 331 bp and also carried the phenicol exporter gene fexA. The optrA gene was functionally expressed in E. faecalis, E. faecium and Staphylococcus aureus. It was detected more frequently in E. faecalis and E. faecium from food-producing animals (20.3% and 5.7%, respectively) than from humans (4.2% and 0.6%, respectively).
  
  
  CONCLUSIONS
  Enterococci with elevated MICs of linezolid and tedizolid should be tested not only for 23S rRNA mutations and the gene cfr, but also for the novel resistance gene optrA.
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China.
authors.forename: Jiachang
authors.initials: J
authors.lastname: Cai
authors.affiliation: Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Neustadt-Mariensee, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.
authors.forename: Lanqing
authors.initials: L
authors.lastname: Cui
authors.affiliation: Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Neustadt-Mariensee, Germany.
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Feßler
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Congming
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.affiliation: Beijing Key Laboratory of Detection Technology for Animal Food Safety, China Agricultural University, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Veterinary Pharmacology, College of Veterinary Medicine, China Agricultural University, Beijing, China sjz@cau.edu.cn.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000031:analogs & derivatives / Q000494:pharmacology*; D016000:Cluster Analysis; D003227:Conjugation, Genetic; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000662:veterinary; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D023303:Oxazolidinones / Q000494:pharmacology*; D010802:Phylogeny; D010957:Plasmids; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014169:Transformation, Bacterial
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D023303:Oxazolidinones; D002701:Chloramphenicol
keywords: enterococci; florfenicol; interspecies transfer; linezolid; plasmids; tedizolid