POSSIBLE ROLE OF INSERTION-SEQUENCE IS257 IN DISSEMINATION AND EXPRESSION OF HIGH-LEVEL AND LOW-LEVEL TRIMETHOPRIM RESISTANCE IN STAPHYLOCOCCI

The transposon-like structure Tn4003 and related elements were found t o encode high- and low-level trimethoprim resistance (Tp(r)) in Staphy lococcus aureus and coagulase-negative staphylococci. By using transcr iptional fusions in Escherichia coil, the variation in resistance leve ls was found to correlate with the transcriptional activity of the reg ion presumed to carry the promoter for the operon containing the Tp(r) dihydrofolate reductase gene, dfrA, encoded by these elements. The re duced transcriptional activities exhibited by elements encoding low-le vel Tp(r) appear to be a consequence of deletions adjacent to the copy of IS257 which normally encodes the -35 sequences of these promoters. The data obtained not only support the involvement of IS257 in the tr anscription of the proposed thyE-dfrA-orf-140 operon of Tn4003 but may also implicate this insertion sequence in the mechanisms resulting in the variation in Tp(r) levels observed in staphylococci.