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Methicillin-resistant  Macrococcus caseolyticus  strains from bovine and canine origins were found to carry a novel  mecD  gene conferring resistance to all classes of β-lactams including anti-MRSA cephalosporins. Association of β-lactam resistance with  mecD  was demonstrated by gene expression in  S. aureus  and deletion of the  mecD -containing island in  M. caseolyticus . The  mecD  gene was located either on an 18,134-bp  M. caseolyticus  resistance island (McRI  mecD  -1) or a 16,188-bp McRI  mecD  -2. Both islands were integrated at the 3′ end of the  rpsI  gene, carried the  mecD  operon ( mecD-mecR1   m   -mecI   m  ), and genes for an integrase of the tyrosine recombinase family and a putative virulence-associated protein ( virE ). Apart from the  mecD  operon, that shared 66% overall nucleotide identity with the  mecB  operon, McRI  mecD   islands were unrelated to any  mecB -carrying elements or staphylococcal cassette chromosome  mec . Only McRI  mecD  -1 that is delimitated at both ends by direct repeats was capable of circular excision. The recombined excision pattern suggests site-specific activity of the integrase and allowed identification of a putative core attachment site. Detection of  rpsI -associated integrases in  Bacillus  and  S. aureus  reveals a potential for broad-host range dissemination of the novel methicillin resistance gene  mecD .

Novel methicillin resistance gene mecD in clinical Macrococcus caseolyticus strains from bovine and canine sources