Analysis of the resistance mediated by several R-factors to Tetracycline and Minocycline

SUMMARY The resistance levels conferred by the T-determinants in four R-factors to Tetracycline and Minocycline in cells of Escherichia coli K 12, before and after induction of maximum resistance by treatment with sub-inhibitory concentrations of the drugs, are measured by simple growth-and-challenge tests. The effect of a plasmid T K which confers tetracycline resistance on its host Klebsiella aerogenes is tested in the same way. The five T-determinants fall into a high-level and a low-level group for resistance, the former giving 3- to 4-fold higher resistance in both induced and uninduced cells than the latter. The T-determinants all confer much lower resistance to Minocycline (a tetracycline molecule modified at the C-6 and C-7 positions) than to Tetracycline. The main cause of this difference is that cells carrying a T-determinant exclude Minocycline much less efficiently than Tetracycline, but in addition Minocycline is less effective than Tetracycline in inducing increased resistance. These results are discussed in the light of a model put forward to explain the inducible nature of R-factor resistance to the tetracyclines.