The mechanism of acquisition of methicillin resistance

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(1) Cloning and determination of three types of SCCmec.beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a nova mobile genetic element, designated staphylococcal cassette chromosome mec(SCCmec)We have cloned and determined the nucleotide sequence of SCCmecs of three strains, NCTC10442(isolated in England in 1961), N315(isolated in Japan in 1982), and 85/2082 (isolatd in New Zieland in 1985). There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. Structural analysis of the new elements revealed that they possessed all the salient features of the SCCmec ; conserved terminal inverted repeats and direct repeats at the integration junction points ; conserved genetic organization around mecA gene ; and the presence of cassette chromosome recombinase(ccr) genes responsible for the movement of SCCmec.(2) Mobility of SCCmec.We have identified two movel genes, ccrA and ccrB, encoding polypeptides having a partial homology to recombinases of the invertase/resolvase family. The open reading frames were found to catalyze precise excision of the SCCmec from the methicillin-resistant S.aureus chromosome and site-specific as well as orientation-specific integration of the SCCmec into the S.aureus chromosome when introduced into the cells as a recombinant multicopy plasmid.