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A mutant of the repressed R factor R1a and two mutants of the derepressed R factor R1drd-19 showing a two- to fourfold increase in resistance to all of the antibiotics to which the wild-type R factors mediate resistance were studied. The increased resistance was due to a two- to fourfold increase in the number of R-factor copies per chromosome. The production of drug-metabolizing enzymes was linearly correlated to the gene dosage. There was also a linear correlation between resistance to the drugs and the production of the corresponding enzymes. The mutations were also expressed inProteus mirabilis PM1. InProteus , R factors are split into two plasmids, resistance transfer factor and the resistance part. The mutation in one of the mutant R factors seems to be located in the resistance part. A second fi+ R factor (R100) was introduced into strains already carrying R1drd-19 or the mutant R factor R1drd-19B2 . In the first case, R100 and R1drd-19 segregated with equal probability when the bacteria were grown on antibiotic-free medium, whereas, in the second case, R100 was rapidly and preferentially excluded.

Mutations in R Factors ofEscherichia coliCausing an Increased Number of R-Factor Copies per Chromosome