Complete Nucleotide Sequence and Comparative Analysis of pPR9, a

We have sequenced the conjugative plasmid pPR9, which carries the ileS2 gene, which had contributed to the dissemination of high-level mupirocin resistance at our institution. The plasmid backbone shows extensive genetic conservation with plasmids belonging to the pSK41/pGO1 family, but comparative analyses have revealed key differences that provide important insights into the evolution of these medically important plasmids and high-level mupirocin resistance in staphylococci and highlight the role of insertion sequence IS257 in these processes. Plasmids carrying the ileS2 gene play an important role in high-level mupirocin resistance (Hi-Mupr) spread and conse-quent clinical and epidemiological problems (8, 17, 23, 26). To date, complete nucleotide sequences of two ileS2-carrying plas-mids have been determined: pUSA03 (37,136 bp; GenBank entry NC_007792) was carried by an epidemic USA300 com-munity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain (10), and a partially annotated sequence is available for pV030-8 (39,041 bp; NC_010279), which was iso