RESISTANCE OF ESCHERICHIA COLI TO TETRACYCLINES

Minocycline (7-dimethylamino-6-demethyl-6-deoxytetracycline) is a new semisynthetic tetracycline with potent activity against tetracycline-susceptible bacterial pathogens and unique activity against tetracycline-resistant staphylococci. Studies to determine the basis for this unique activity showed that, whereas tetracycline-resistant staphylococci took up less 3H-tetracycline than the susceptible cells, both the tetracycline-resistant and -susceptible cells accumulated equivalent amounts of "C-minocycline. In contrast, tetracyclineresistant Escherichia coli cells were relatively resistant to minocycline and accumulated less of both drugs than did the susceptible organisms. It is proposed that minocycline is effective against tetracycline-resistant staphylococci because of its ability to penetrate the cells sufficiently to reach inhibiting concentrations at sensitive reaction sites.

“…Several investigators have shown that tetracycline uptake is diminished in resistant strains (3,6,10,17,19). This report deals.…”

mentioning

confidence: 82%

Uptake of Minocycline and Tetracycline by Tetracycline-Susceptible and -Resistant Bacteria

Kuck¹,

Forbes²

1973

“…Studies of tetracycline metabolism have demonstrated active uptake ofthe drug into sensitive cells (1,15). However, the amounts of drug taken up by different strains of Escherichia coli did.…”

mentioning

confidence: 99%

Two Transport Systems for Tetracycline in Sensitive Escherichia coli : Critical Role for an Initial Rapid Uptake System Insensitive to Energy Inhibitors

McMurry¹,

Levy

1978

Escherichia coli sensitivity to tetracycline involves transport and accumulation of the antibiotic within the cell by two different uptake systems: an initial rapid uptake, which occun over the initial 6 min of contact of the cell with tetracycline, and a slower uptake system, which continues indefinitely and whose rate of uptake is 1/10 that of the rapid system. Only the slow uptake system is blocked by inhibitors of energy-driven systems; it appears to be particularly dependent upon energy from oxidative phosphorylation. Althoughboth uptake systems lead to accumulation ofintracellular tetracycline and contribute to the cell's sensitivity, the rapid uptake system appears to be the more important. While these studies confirm active transport of tetracycline into the cell, they demonstrate that a critical uptake system which appears insensitive to metabolic inhibitors occurs initially.The tetracyclines are effective bacteriostatic antimicrobial agents. They were introduced in the beginning of the 1950s and received widespread acceptance because of their broad-spectrum activity against gram-negative as well as gram-positive bacterial infections (17). The drugs inhibit protein synthesis by interfering with the binding of aminoacyl tRNA to the ribosome-mRNA complex (36). The site of action of the drug appears to be codon-anticodon recognition (19).Studies of tetracycline metabolism have demonstrated active uptake ofthe drug into sensitive cells (1, 15). However, the amounts of drug taken up by different strains of Escherichia coli did. not correlate with levels of sensitivity (32). We have been particularly interested in this property because we are concemed with the mechanism of resistance to tetracycline, particularly that mediated by plasmids (24,25,27). For this reason we have investigated in more detail the mechanism by which tetracycline is accumulated in sensitive cells. From these studies we have determined that the sensitive cell has two uptake systems for tetracycline, only one of which appears sensitive to metabolic inhibitors. An initial uptake occurs, which appears to reach an equilibrium with the tetracycline in the medium after 6 min. A slow, second uptake system then is evident, which accumulates tetracycline over a period of hours. It is the slow uptake system that is sensitive to energy inhibitors.Experiments with mutants uncoupled in oxidative phosphorylation confimned the presence of two uptake systems and indicated that sensitivity to the drug can be conferred by the rapid uptake system alone.MATERIALS AND METLODS

“…R-factor-mediated resistance to tetracycline has been shown to involve an altered bacterial permeability to the antibiotic (2,3) and a similar mechanism has been proposed for sulfonamide resistance in gram-negative organisms (8). Up to this time, however, all R-factor-mediated resistance to penicillins and cephalosporins has been thought to involve ,8-lactamase production (12) with a consequent destruction of the antibiotics.…”

mentioning

confidence: 99%

Effect of R-Factor-Mediated Genes on Some Surface Properties of Escherichia coli

Curtis

Richmond

1974

The plasmid RP1 was shown to contain a genetic region (the irp region) responsible for influencing the intrinsic resistance of Escherichia coli to penicillins but not to cephalosporins. Mutants in whic"h the irp genes are inactive were isolated. RP1 carrying functional irp genes protected E. coli AS19 against lysozyme lysis and also enhanced resistance to actinomycin D, to nalidixic acid, and to rifampin. This plasmid also phenotypically repaired the hypersensitivity to penicillins of strain AS19, and also that of E. coli envA mutants. Similar regions were not detected on the plasmids Rl and R55.