title: Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius.
abstract: OBJECTIVE
  MDR methicillin-resistant Staphylococcus pseudintermedius (MRSP) strains have emerged rapidly as major canine pathogens and present serious treatment issues and concerns to public health due to their, albeit low, zoonotic potential. A further understanding of the genetics of resistance arising from a broadly susceptible background of S. pseudintermedius is needed.
  
  
  METHODS
  We sequenced the genomes of 12 S. pseudintermedius isolates of varied STs and resistance phenotypes.
  
  
  RESULTS
  Nine distinct clonal lineages had acquired either staphylococcal cassette chromosome (SCC) mec elements and/or Tn5405-like elements carrying up to five resistance genes [aphA3, sat, aadE, erm(B), dfrG] to generate MRSP, MDR methicillin-susceptible S. pseudintermedius and MDR MRSP populations. The most successful and clinically problematic MDR MRSP clones, ST68 SCCmecV(T) and ST71 SCCmecII-III, have further accumulated mutations in gyrA and grlA conferring resistance to fluoroquinolones. The carriage of additional mobile genetic elements (MGEs) was highly variable, suggesting that horizontal gene transfer is frequent in S. pseudintermedius populations.
  
  
  CONCLUSIONS
  Importantly, the data suggest that MDR MRSP evolved rapidly by the acquisition of a very limited number of MGEs and mutations, and that the use of many classes of antimicrobials may co-select for the spread and emergence of MDR and XDR strains. Antimicrobial stewardship will need to be comprehensive, encompassing human medicine and veterinary disciplines to successfully preserve antimicrobial efficacy.
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McCarthy
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Ewan M
authors.initials: EM
authors.lastname: Harrison
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Kinga
authors.initials: K
authors.lastname: Stanczak-Mrozek
authors.affiliation: Pathobiology Unit, University Veterinary Hospital, School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Leggett
authors.affiliation: Centre of Preventive Medicine, Animal Health Trust, Newmarket, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Waller
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Holmes
authors.affiliation: Veterinary Clinical Sciences and Services, Royal Veterinary College, Hawkshead Campus, University of London, London, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Lloyd
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lindsay
authors.affiliation: Veterinary Clinical Sciences and Services, Royal Veterinary College, Hawkshead Campus, University of London, London, UK aloeffler@rvc.ac.uk.
authors.forename: Anette
authors.initials: A
authors.lastname: Loeffler
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005075:Biological Evolution; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D006801:Humans; D020071:Interspersed Repetitive Sequences; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D013210:Staphylococcus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial
keywords: MRSP; antimicrobial resistance; horizontal gene transfer; whole-genome sequencing; zoonotic