Evolutionary Origin of the Staphylococcal Cassette Chromosome <i>mec</i> (SCC <i>mec</i> )

Abstract

Several lines of evidence indicate that the most primitive staphylococcal species, those of the <i>Staphylococcus sciuri</i> group, were involved in the first stages of evolution of the staphylococcal cassette chromosome <i>mec</i> (SCC<i>mec</i>), the genetic element carrying the β-lactam resistance gene <i>mecA</i> However, many steps are still missing from this evolutionary history. In particular, it is not known how <i>mecA</i> was incorporated into the mobile element SCC prior to dissemination among <i>Staphylococcus aureus</i> and other pathogenic staphylococcal species. To gain insights into the possible contribution of several species of the <i>Staphylococcus sciuri</i> group to the assembly of SCC<i>mec</i>, we sequenced the genomes of 106 isolates, comprising <i>S. sciuri</i> (<i>n</i> = 76), <i>Staphylococcus vitulinus</i> (<i>n</i> = 18), and <i>Staphylococcus fleurettii</i> (<i>n</i> = 12) from animal and human sources, and characterized the native location of <i>mecA</i> and the SCC insertion site by using a variety of comparative genomic approaches. Moreover, we performed a single nucleotide polymorphism (SNP) analysis of the genomes in order to understand SCC<i>mec</i> evolution in relation to phylogeny. We found that each of three species of the <i>S. sciuri</i> group contributed to the evolution of SCC<i>mec</i>: <i>S. vitulinus</i> and <i>S. fleurettii</i> contributed to the assembly of the <i>mec</i> complex, and <i>S. sciuri</i> most likely provided the mobile element in which <i>mecA</i> was later incorporated. We hypothesize that an ancestral SCC<i>mec</i> III cassette (an element carried by one of the most epidemic methicillin-resistant <i>S. aureus</i> clones) originated in <i>S. sciuri</i> possibly by a recombination event in a human host or a human-created environment and later was transferred to <i>S. aureus</i>.