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.

Findings: 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.

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 mecA(LGA251).

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

Figure 1

Comparison of the type XI SCCmec of LGA251 with other SCC elements Schematic diagram of type II SCCmec of meticillin-resistant Staphylococcus aureus MRSA252 (top), type IV SCCmec of MW2 (upper middle), type XI SCCmec of LGA251 (lower middle), and the SCCmec-like element of Macrococcus caseolyticus JCSC7096 (bottom). The names of the coding sequences associated with drug and metal resistance are provided. Coding sequences are marked in the direction of transcription as arrows. Coding sequences belonging to the mec and ccr complexes, and IS431 are coloured, with homologues given the same colour; the individual genes belonging to these groups are named. Light pink shading joins regions that are conserved between elements. The coloured boxes at the end of the SCC elements mark the integration site sequence (blue, attL; green attR).

Figure 2

Geographical distribution of the bovine and human meticillin-resistant Staphylococcus aureus strains carrying the mecA_LGA251 gene in England The colouring of the symbols and labels indicates common lineage, defined on the basis of spa typing, multilocus sequence typing, or both. spa types and multilocus sequence types are indicated in the labels.