SUMMARY Trimethoprim-resistant mutants ofE. coliK12 have been isolated by-serial subculture in progressively higher concentrations of trimethoprim. High-level resistance depends on the accumulation of several mutational changes. Transduction with bacteriophage P1 has shown that all the mutations involved in resistance are associated with a locus, to be calledtmr, betweenpyr AandpdxAand closely linked topdxA. Resistance is accompanied by, and presumably due to, an increased activity of the target enzyme, dihydrofolate reductase. Thetmrlocus may include the structural gene for dihydrofolate reductase but the only mutations that have so far been observed are concerned with regulation.
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Breeze et al. (1975) studied this question.
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