The ␤-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecAcarrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.

Molecular cloning and nucleotide sequence analysis were performed for the identification of the regulator genes of mclhicillin resistance in the genome of a MRSA strain N3 15. Two open reading frames (orfs) were identified in the S'-Banking region of the rrrecA gene. Predicted amino acid sequences of these ork showed exlcnsive homology to the co-inducer and the repressor protein of the pcnicillinasc (P&se) production in Sruphyrylocaccws uttreus m well as in &~aci~lrrs h'cltattjlmtis. These orfs are considered to encode putative co-inducer and repressor proteins specific for the regulation of methicillin resistance in MRSA./nrrA; Repressor; Co-inducer; Methicillin rcsistancc; Stupltylococcus auretts

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Methicillin-resistant Staphylococcus aureus (MRSA) has two mechanisms of resistance to beta-lactam antibiotics; one is mediated by mecA gene expression, and the other by penicillinase production. It has been generally accepted in the clinical field that beta-lactam antibiotics are not the drugs of choice for MRSA infection. In this report, however, ampicillin and penicillin G were shown to have relatively good activity against MRSA if combined with a beta-lactamase inhibitor, sulbactam. These beta-lactam antibiotics were found to have relatively high binding affinities to PBP2', the mecA-encoded MRSA-specific penicillin-binding protein. The possible therapeutic application of sulbactam/ampicillin against MRSA infection in combination with arbekacin, an aminoglycoside antibiotic newly developed and introduced into clinical use in Japan, is discussed.