Characterization of SCC mec Instability in Methicillin-Resistant Staphylococcus aureus Affecting Adjacent Chromosomal Regions, Including the Gene for Staphylococcal Protein A ( spa ).

Staphylococcal cassette chromosome mec (SCC mec ) represents a sequence of clear clinical and diagnostic importance in staphylococci. At a minimum the chromosomal cassette contains the mecA gene encoding PBP2a but frequently also includes additional antibiotic resistance genes (e.g., ermA and aadC ; macrolide and aminoglycoside resistance, respectively). Certain regions within SCC mec elements are hot spots for sequence instability due to cassette-specific recombinases and a variety of internal mobile elements. SCC mec changes may affect not only cassette stability but the integrity of adjacent chromosomal sequences (e.g., the staphylococcal protein A gene; spa ). We investigated SCC mec stability in methicillin-resistant Staphylococcus aureus (MRSA) strains carrying one of four SCC mec types cultured in the absence of antimicrobial selection over a 3-month period. SCC mec rearrangements were first detected in cefoxitin-susceptible variants after 2 months of passage, and most commonly showed precise excision of the SCC mec element. Sequence analysis after 3 months revealed both precise SCC mec excision and a variety of SCC mec internal deletions, some including extensive adjacent chromosomal loss, including spa . No empty cassettes (i.e., loss of just mecA from SCC mec ) were observed among the variants. SCC mec stability was influenced both by internal mobile elements (IS 431 ) as well as the host cell environment. Genotypically similar clinical isolates with deletions in the spa gene were also included for purposes of comparison. The results indicate a role for host-cell influence and the IS 431 element on SCC mec stability.