NEW DHFRVIII TRIMETHOPRIM-RESISTANCE GENE, FLANKED BY IS26, WHOSE PRODUCT IS REMOTE FROM OTHER DIHYDROFOLATE REDUCTASES IN PARSIMONY ANALYSIS

A new plasmid-borne gene, dhfrVIII, encoding high-level trimethoprim r esistance (Tp(R)) was found in an intestinal Escherichia coli. It seem s to be a widely occurring mediator of Tp(R). Among 973 examined Tp(R) E. coli, the new resistance gene was found in 13 (1.3%) isolates from Sweden, Finland and Nigeria, The new gene was sequenced and found to code for a dihydrofolate reductase (DHFR) of 169 amino acids (M(r) 19 005). The dhfrVIII gene on the studied plasmid pLM0226 was observed to be flanked by IS26 elements. The dhfrVIII gene and a 3' unidentified open reading frame (ORF) seem to be borne on a compound transposon wit h IS26 at its ends, since the configuration of two IS26 flanking dhfrV III and the unidentified ORF was conserved among the isolates that wer e probe-positive for the gene, Phylogeny parsimony analysis showed the dhfrVIII-encoded enzyme to be only remotely related to other known pl asmid-mediated, drug-resistant DHFR. Only a few of the latter form wel l-supported monophyletic groups.