The Staphylococcus aureus mec Determinant Comprises an Unusual Cluster of Direct Repeats and Codes for a Gene Product Similar to the Escherichia coli sn-Glycerophosphoryl

The DNA sequence located between mecA, the gene that codes for penicillin-binding protein PBP2', and insertion sequence-like element IS431mec has been termed hypervariable because of its length polymorphism among different staphylococcal isolates. We sequenced and characterized the hypervariable region of the methicillin resistance determinant (mec) isolated from Staphylococcus aureus BB270. Within the 2,040-bp hypervariable region, we identified an unusual accumulation of long direct repeats. Analysis of the DNA sequence revealed a minimal direct repeat unit (dru) of 40 bp which was repeated 10 times within 500 bp. The dru sequences are responsible for the length polymorphism of mec. Moreover, we identified an open reading frame that codes for 145 amino acids (0RF145), whose deduced amino acid sequence showed 57 % amino acid sequence similarity to the N terminus of the glycerophosphoryl diester phosphodiesterase (UgpQ) of Escherichia coli. The methicillin resistance (Mc') determinant (mec) is responsible for the intrinsic resistance of staphylococci to penicillinase-resistant 3-lactam antibiotics (21, 41, 45). The mec DNA is over 30 kb long and integrates into a specific site of the SmaI G fragment of the Staphylococcus aureus NCT