Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate

Ilan Rosenshine, Tal Zusman, Ruth Werczberger, Moshe Mevarech

Research output: Contribution to journalArticlepeer-review

Abstract

The archaebacterium Halobacterium volcanii was found to be very sensitive to the antifolate drugs trimethoprim and methotrexate. Resistant mutants arise spontaneously at a frequency of 10-10-10-9. The following evidence is presented which correlates the spontaneous resistance to gene amplification: (a) all resistant mutants have readily observable amplified DNA sequences; (b) the amplified DNA shares common sequences; (c) resistant mutants revert at high frequency to sensitivity, at the same time losing the amplified sequences; (d) there is a genetic linkage between the resistance to trimethoprim and the amplified DNA sequences; (e) all resistant mutants overproduce a 20 kDa protein that corresponds in size to the enzyme dihydrofolate reductase the target of the drugs.

Original languageEnglish
Pages (from-to)518-522
Number of pages5
JournalMolecular Genetics and Genomics
Volume208
Issue number3
DOIs
StatePublished - Jul 1987

Keywords

  • Archaebacterium
  • DHFR
  • DNA amplification
  • Halobacterium
  • Trimethoprim

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