Skip to main content
NCBI home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1987 Sep;169(9):4119–4123. doi: 10.1128/jb.169.9.4119-4123.1987

5-Fluorouracil-resistant strain of Methanobacterium thermoautotrophicum.

D P Nagle Jr, R Teal, A Eisenbraun
PMCID: PMC213717  PMID: 3624203

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.

Full text

PDF
4119

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BROCKMAN R. W., DAVIS J. M., STUTTS P. Metabolism of uracil and 5-fluorouracil by drug-sensitive and by drug-resistant bacteria. Biochim Biophys Acta. 1960 May 6;40:22–32. doi: 10.1016/0006-3002(60)91311-1. [DOI] [PubMed] [Google Scholar]
  2. Balch W. E., Fox G. E., Magrum L. J., Woese C. R., Wolfe R. S. Methanogens: reevaluation of a unique biological group. Microbiol Rev. 1979 Jun;43(2):260–296. doi: 10.1128/mr.43.2.260-296.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balch W. E., Wolfe R. S. Transport of coenzyme M (2-mercaptoethanesulfonic acid) in Methanobacterium ruminantium. J Bacteriol. 1979 Jan;137(1):264–273. doi: 10.1128/jb.137.1.264-273.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beck C. F., Ingraham J. L., Neuhard J., Thomassen E. Metabolism of pyrimidines and pyrimidine nucleosides by Salmonella typhimurium. J Bacteriol. 1972 Apr;110(1):219–228. doi: 10.1128/jb.110.1.219-228.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Dalke P., Magill J. M. Specificity of uracil uptake in Neurospora crassa. J Bacteriol. 1979 Jul;139(1):212–219. doi: 10.1128/jb.139.1.212-219.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Diekert G., Jaenchen R., Thauer R. K. Biosynthetic evidence for a nickel tetrapyrrole structure of factor F430 from Methanobacterium thermoautotrophicum. FEBS Lett. 1980 Sep 22;119(1):118–120. doi: 10.1016/0014-5793(80)81011-8. [DOI] [PubMed] [Google Scholar]
  8. GRIPPO P., IACCARINO M., ROSSI M., SCARANO E. THIN-LAYER CHROMATOGRAPHY OF NUCLEOTIDES, NUCLEOSIDES AND NUCLEIC ACID BASES. Biochim Biophys Acta. 1965 Jan 11;95:1–7. doi: 10.1016/0005-2787(65)90204-2. [DOI] [PubMed] [Google Scholar]
  9. Gilles H., Thauer R. K. Uroporphyrinogen III, an intermediate in the biosynthesis of the nickel-containing factor F430 in Methanobacterium thermoautotrophicum. Eur J Biochem. 1983 Sep 1;135(1):109–112. doi: 10.1111/j.1432-1033.1983.tb07624.x. [DOI] [PubMed] [Google Scholar]
  10. Grenson M. The utilization of exogenous pyrimidines and the recycling of uridine-5'-phosphate derivatives in Saccharomyces cerevisiae, as studied by means of mutants affected in pyrimidine uptake and metabolism. Eur J Biochem. 1969 Dec;11(2):249–260. doi: 10.1111/j.1432-1033.1969.tb00767.x. [DOI] [PubMed] [Google Scholar]
  11. Heidelberger C., Danenberg P. V., Moran R. G. Fluorinated pyrimidines and their nucleosides. Adv Enzymol Relat Areas Mol Biol. 1983;54:58–119. [PubMed] [Google Scholar]
  12. Hook E. W., 3rd, Baker-Zander S. A., Moskovitz B. L., Lukehart S. A., Handsfield H. H. Ceftriaxone therapy for asymptomatic neurosyphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy. Sex Transm Dis. 1986 Jul-Sep;13(3 Suppl):185–188. [PubMed] [Google Scholar]
  13. Jones G. E. 6-azauracil-resistant variants of cultured plant cells lack uracil phosphoribosyltransferase activity. Plant Physiol. 1984 May;75(1):161–165. doi: 10.1104/pp.75.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones W. J., Nagle D. P., Jr, Whitman W. B. Methanogens and the diversity of archaebacteria. Microbiol Rev. 1987 Mar;51(1):135–177. doi: 10.1128/mr.51.1.135-177.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McIvor R. S., Wohlhueter R. M., Plagemann P. G. Uracil phosphoribosyltransferase from Acholeplasma laidlawii: partial purification and kinetic properties. J Bacteriol. 1983 Oct;156(1):192–197. doi: 10.1128/jb.156.1.192-197.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meile L., Kiener A., Leisinger T. A plasmid in the archaebacterium Methanobacterium thermoautotrophicum. Mol Gen Genet. 1983;191(3):480–484. doi: 10.1007/BF00425766. [DOI] [PubMed] [Google Scholar]
  17. Natalini P., Ruggieri S., Santarelli I., Vita A., Magni G. Baker's yeast UMP:pyrophosphate phosphoribosyltransferase. Purification, enzymatic and kinetic properties. J Biol Chem. 1979 Mar 10;254(5):1558–1563. [PubMed] [Google Scholar]
  18. O'Donovan G. A., Neuhard J. Pyrimidine metabolism in microorganisms. Bacteriol Rev. 1970 Sep;34(3):278–343. doi: 10.1128/br.34.3.278-343.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rasmussen U. B., Mygind B., Nygaard P. Purification and some properties of uracil phosphoribosyltransferase from Escherichia coli K12. Biochim Biophys Acta. 1986 Apr 11;881(2):268–275. doi: 10.1016/0304-4165(86)90013-9. [DOI] [PubMed] [Google Scholar]
  20. Reeve A., Shulman S. A., Zimmerman A. W., Cassidy S. B. Methylphenidate therapy for aggression in a man with ring 22 chromosome. Report and literature review. Arch Neurol. 1985 Jan;42(1):69–72. doi: 10.1001/archneur.1985.04060010075019. [DOI] [PubMed] [Google Scholar]
  21. Santoro N., Konisky J. Characterization of bromoethanesulfonate-resistant mutants of Methanococcus voltae: evidence of a coenzyme M transport system. J Bacteriol. 1987 Feb;169(2):660–665. doi: 10.1128/jb.169.2.660-665.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smith M. R. Reversal of 2-bromoethanesulfonate inhibition of methanogenesis in Methanosarcina sp. J Bacteriol. 1983 Nov;156(2):516–523. doi: 10.1128/jb.156.2.516-523.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Whitman W. B., Ankwanda E., Wolfe R. S. Nutrition and carbon metabolism of Methanococcus voltae. J Bacteriol. 1982 Mar;149(3):852–863. doi: 10.1128/jb.149.3.852-863.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES