Summary
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.
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Communicated by A. Böck
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Rosenshine, I., Zusman, T., Werczberger, R. et al. Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate. Mol Gen Genet 208, 518–522 (1987). https://doi.org/10.1007/BF00328149
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DOI: https://doi.org/10.1007/BF00328149