Analysis of Mec Regulator Genes in Clinical Methicillin-resistant Staphylococcus aureus Isolates according to the Production of Coagulase, Types of Enterotoxin, and Toxic Shock Syndrome Toxin-1

The intrinsic resistance of methicillin-resistant Staphylococcus aureus (MRSA) is frequently explained by the production of an additional penicillin-binding protein (PEP), which is encoded by the mecA gene. The mec regulator genes, mecR1 and mecI, was identified in mecA-carrying Staphylococcus aureus N315. Between February and March, 1993, 179 clinical MRSA isolates were collected from institutions in Hiroshima prefecture. According to serological types of coagulase, enterotoxins, and toxic shock syndrome toxin-1 (TSST-1) productions, these strains were classified into 6 groups. In 53 strains chosen from all groups, mec regulatory gene distributions were divided into two groups; one with whole regulatory genes and another with the lacking region, including 3'-partial region of the mecR1 gene and mecI gene. This same deletion was detected across the different groups, suggesting that the deletion occurred at the ancestral strain before branching according to coagulase or enterotoxin productions. The strains with this lacking region showed a high-level of resistance to methicillin, while the strains with whole regulatory genes consisted of low and high levels of resistant strains. The highly resistant strains with whole regulatory genes were found to harbor a point mutation in the mecI gene. The basal levels of mecA gene transcription were elevated in the strains with the lacking region or the mecI point mutations. These data suggest that deletion or mutation of the mecI gene, the repressor on the mecA gene, might play an important role in methicillin resistance in clinical isolates of MRSA.