Action of 12 Tetracyclines on Susceptible and Resistant Strains of Staphylococcus aureus

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Abstract
The relative growth inhibition caused by 12 tetracyclines in a susceptible strain of Staphylococcus aureus (111-elim) and in the same strain carrying a resistance-plasmid (111) showed entirely different patterns. For four of the tetracyclines (minocycline, anhydrotetracycline, chelocardin, and desdimethylaminotetracycline), the strain with the tetracycline plasmid (111) had virtually the same tolerance as the susceptible strain (111-elim). A resistant mutant of strain 111-elim showed a third pattern of relative growth inhibition, and another distinct pattern was observed in a veterinary wild strain of S. aureus. Of the 12 tetracyclines, 11 were effective inducers of higher tetracycline resistance in S. aureus 111, but no correlation was found between the efficacy of the tetracyclines as inducers and as inhibitors of growth of 111-elim or 111. At external drug concentrations causing doubling of the generation time (Ki), 111-elim accumulated tetracycline, oxytetracycline, and minocycline to a degree corresponding to several thousand molecules per coccus. At a fixed external drug concentration, 111 accumulated less tetracycline and oxytetracycline than 111-elim, whereas comparison at their respective Ki values showed accumulation to be significantly higher for 111 than for 111-elim. The accumulation of tetracyclines is assumed to involve both surface sorption and active membrane transport. Resistance is probably due to decreased accumulation of the drugs, and a hypothesis explaining the mechanism of resistance is offered.