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 language | English |
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Pages (from-to) | 518-522 |
Number of pages | 5 |
Journal | Molecular Genetics and Genomics |
Volume | 208 |
Issue number | 3 |
DOIs | |
State | Published - Jul 1987 |
Keywords
- Archaebacterium
- DHFR
- DNA amplification
- Halobacterium
- Trimethoprim