TETRACYCLINES are broad-spectrum bacteriostatic antibiotics which act by inhibiting protein synthesis1,2. However, their usefulness in combating bacterial infection has been sharply curtailed by the widespread occurrence in bacteria of tetracycline resistance encoded by genes located on extrachromosomal DNA elements called plasmids3,4. In many bacteria, notably Enterobacteriaceae, Pseudomonas and Staphylococcus, plasmid-mediated tetracycline resistance is inducible; the resistance level can be increased by preincubation of the cells in sub-inhibitory amounts of tetracycline5–8. Coincident with induced resistance is the induced synthesis of a plasmid-encoded inner membrane protein which we have designated TET protein8–10. Synthesis of this protein (and presumably most of the resistance determinant) is negatively regulated; a represser has been partially purified11. However, the mechanisms for plasmid-mediated tetracycline resistance are not yet clear, and there seems to be no degradation of the antibiotic in resistant cells10,12,13. Although resistant cells accumulate less tetracycline than do sensitive cells14,15, the moderately reduced uptake does not explain the much larger difference in sensitivity to the drug10,16,17. We report here that plasmid-containing resistant cells take up tetracycline by a different transport mechanism from that of sensitive cells. This altered transport seems to be responsible for at least part of the difference in tetracycline inhibition of sensitive as compared to resistant cells.
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LEVY, S., MCMURRY, L. Plasmid-determined tetracycline resistance involves new transport systems for tetracycline. Nature 276, 90–92 (1978). https://doi.org/10.1038/276090a0
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