title: A new dhfrVIII trimethoprim-resistance gene, flanked by IS26, whose product is remote from other dihydrofolate reductases in parsimony analysis.
abstract: A new plasmid-borne gene, dhfrVIII, encoding high-level trimethoprim resistance (TpR) was found in an intestinal Escherichia coli. It seems to be a widely occurring mediator of TpR. Among 973 examined TpR 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) 19005). The dhfrVIII gene on the studied plasmid pLMO226 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 with IS26 at its ends, since the configuration of two IS26 flanking dhfrVIII and the unidentified ORF was conserved among the isolates that were probe-positive for the gene. Phylogeny parsimony analysis showed the dhfrVIII-encoded enzyme to be only remotely related to other known plasmid-mediated, drug-resistant DHFR. Only a few of the latter form well-supported monophyletic groups.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Sundström
authors.forename: C
authors.initials: C
authors.lastname: Jansson
authors.forename: K
authors.initials: K
authors.lastname: Bremer
authors.forename: E
authors.initials: E
authors.lastname: Heikkilä
authors.forename: B
authors.initials: B
authors.lastname: Olsson-Liljequist
authors.forename: O
authors.initials: O
authors.lastname: Sköld
mesh_terms: D000595:Amino Acid Sequence; D000828:Animal Population Groups / Q000235:genetics; D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D001435:Bacteriophages / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D004251:DNA Transposable Elements; D004926:Escherichia coli / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D010944:Plants / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014296:Trimethoprim Resistance / Q000235:genetics*; D015003:Yeasts / Q000201:enzymology / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D013762:Tetrahydrofolate Dehydrogenase