Laura García-Álvarez PhD a, Matthew TG Holden PhD b, Heather Lindsay BSc a, Cerian R Webb PhD a, Derek FJ Brown PhD c, Martin D Curran PhD c, Enid Walpole FIMLS c, Karen Brooks BSc b, Derek J Pickard PhD b, Christopher Teale MRCVS d, Prof Julian Parkhill PhD b, Stephen D Bentley PhD b, Giles F Edwards FRCPath e, E Kirsty Girvan MSc e, Angela M Kearns PhD f, Bruno Pichon PhD f, Robert LR Hill PhD f, Anders Rhod Larsen PhD g, Robert L Skov MD g, Prof Sharon J Peacock PhD h, Prof Duncan J Maskell PhD a, Dr Mark A Holmes VetMB a. The Lancet Infectious Diseases, Volume 11, Issue 8, Pages 595 - 603, August 2011. Published Online: 03 June 2011
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.

Findings
A divergent mecA homologue (mecALGA251) was discovered in the LGA251 genome located in a novel staphylococcal cassette chromosome mec element, designated type-XI SCCmec. The mecALGA251 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 mecALGA251 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.

Interpretation
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 mecALGA251.

Funding
Department for Environment, Food and Rural Affairs, Higher Education Funding Council for England, Isaac Newton Trust (University of Cambridge), and the Wellcome Trust.

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