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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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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