title: Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study.
abstract: BACKGROUND
  Animals can act as a reservoir and source for the emergence of novel meticillin-resistant Staphylococcus aureus (MRSA) clones in human beings. Here, we report the discovery of a strain of S aureus (LGA251) isolated from bulk milk that was phenotypically resistant to meticillin but tested negative for the mecA gene and a preliminary investigation of the extent to which such strains are present in bovine and human populations.
  
  
  METHODS
  Isolates of bovine MRSA were obtained from the Veterinary Laboratories Agency in the UK, and isolates of human MRSA were obtained from diagnostic or reference laboratories (two in the UK and one in Denmark). From these collections, we searched for mecA PCR-negative bovine and human S aureus isolates showing phenotypic meticillin resistance. We used whole-genome sequencing to establish the genetic basis for the observed antibiotic resistance.
  
  
  RESULTS
  A divergent mecA homologue (mecA(LGA251)) was discovered in the LGA251 genome located in a novel staphylococcal cassette chromosome mec element, designated type-XI SCCmec. The mecA(LGA251) was 70% identical to S aureus mecA homologues and was initially detected in 15 S aureus isolates from dairy cattle in England. These isolates were from three different multilocus sequence type lineages (CC130, CC705, and ST425); spa type t843 (associated with CC130) was identified in 60% of bovine isolates. When human mecA-negative MRSA isolates were tested, the mecA(LGA251) homologue was identified in 12 of 16 isolates from Scotland, 15 of 26 from England, and 24 of 32 from Denmark. As in cows, t843 was the most common spa type detected in human beings.
  
  
  CONCLUSIONS
  Although routine culture and antimicrobial susceptibility testing will identify S aureus isolates with this novel mecA homologue as meticillin resistant, present confirmatory methods will not identify them as MRSA. New diagnostic guidelines for the detection of MRSA should consider the inclusion of tests for mecA(LGA251).
  
  
  BACKGROUND
  Department for Environment, Food and Rural Affairs, Higher Education Funding Council for England, Isaac Newton Trust (University of Cambridge), and the Wellcome Trust.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Álvarez
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.forename: Heather
authors.initials: H
authors.lastname: Lindsay
authors.forename: Cerian R
authors.initials: CR
authors.lastname: Webb
authors.forename: Derek F J
authors.initials: DF
authors.lastname: Brown
authors.forename: Martin D
authors.initials: MD
authors.lastname: Curran
authors.forename: Enid
authors.initials: E
authors.lastname: Walpole
authors.forename: Karen
authors.initials: K
authors.lastname: Brooks
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Pickard
authors.forename: Christopher
authors.initials: C
authors.lastname: Teale
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Giles F
authors.initials: GF
authors.lastname: Edwards
authors.forename: E Kirsty
authors.initials: EK
authors.lastname: Girvan
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kearns
authors.forename: Bruno
authors.initials: B
authors.lastname: Pichon
authors.forename: Robert L R
authors.initials: RL
authors.lastname: Hill
authors.forename: Anders Rhod
authors.initials: AR
authors.lastname: Larsen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Skov
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: Mark A
authors.initials: MA
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002353:Carrier State / Q000382:microbiology / Q000662:veterinary*; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics / Q000382:microbiology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D003718:Denmark; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D008892:Milk / Q000382:microbiology; D008969:Molecular Sequence Data; D046915:Penicillin-Binding Proteins; D016133:Polymerase Chain Reaction / Q000662:veterinary; D013203:Staphylococcal Infections / Q000235:genetics / Q000382:microbiology / Q000662:veterinary*; D006113:United Kingdom
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins; C487789:mecA protein, Staphylococcus aureus