When strains harboring R factor and showing ampicillin (APC) resistance were inoculated on plates containing various concentrations of APC, mutants carrying various levels of APC resistance occurred at high frequencies. Increases in the level of APC resistance were due to a quantitative increase in the formation of penicillinase. By conjugation experiments and transduction analysis, the mutation was found to affect the gene (amp) governing APC resistance on the R factor. The R-factor mutants carrying high and stable APC resistance were conjugally transferred at the same frequency as their parent R factors, and the level of their resistance to drugs other than APC was not distinct from that conferred by their parents. Such R-factor mutants could easily be obtained from wild-type R factors carrying low APC resistance. The hypersynthesis of penicillinase by such R-factor mutants was considered to be due to the replication of the amp gene on the R factor at hyper-rates and the integration of multiple copies of the amp gene (amp-hyper) in the R-factor genome.
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