title: 5-Fluorouracil-resistant strain of Methanobacterium thermoautotrophicum.
abstract: Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14C-labeled uracil or FU by the two strains was compared, the wild type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype.
mesh_terms: D004352:Drug Resistance, Microbial; D019605:Euryarchaeota / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D010430:Pentosyltransferases / Q000378:metabolism
chemical_list: D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D005472:Fluorouracil