A strain of
Staphylococcus aureus resistant to oxytetracycline and cross-resistant to tetracycline was isolated and the mechanism of its resistance to the drug was studied.
1. The incorporation of amino acids-U-
14C into the protein fraction decreased in the sensitive cells upon addition of oxytetracycline (10μg/ml), while no remarkable influence was observed in the resistant cells. On the other hand, the incorporations of amino acids-U-
14C into the protein fraction with the cell-free extracts from the sensitive as well as the resistant cells were equally inhibited by tetracycline.
2. The uptake of radioactive tetracycline by the sensitive cells was much higher than that by the resistant cells. In order to investigate the mechanism of the decrease in the permeability of the cells to the drug, the intracellular concentration of tetracycline was estimated from the uptake of the drug and its inhibitory effect on the protein biosynthesis in the intact cells. Permeability of the resistant cells to the drug was found to decrease to about 1/100 of that of the sensitive ones and a large part of the drug taken up by the resistant cells seemed to be non-specifically bound to the cellular surface.
3. At low concentrations of tetracycline, its uptake by the sensitive cells was decreased by lowering the temperature or by the addition of energy poisons such as azide, while the uptake by the resistant ones was not much affected. At high concentrations of tetracycline, on the other hand, its uptake by the resistant cells was inhibited by azide as in the sensitive cells.
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