Accumulation of Tetracyclines by Escherichia coli

Abstract

The net accumulation of tetracyclines by Escherichia coli as a function of concentration was shown to be biphasic. At concentrations less than the bacteriostatic levels, the mode of uptake was not azide-sensitive and was considered to be physical adsorption on the cell surface. At concentrations above the minimal inhibitory level, a second, azide-sensitive, uptake component was functional in addition to the surface adsorption process. This second energy-requiring mode was judged to represent penetration of the cytoplasmic membrane by tetracycline molecules to their sites of inhibitory action. Each mode for a given tetracycline and culture is expressed algebraically by a characteristic Freundlich equation. Resistance in E. coli is shown to be a result of diminished transport of antibiotic. However, this resistance was due not to a reduction or loss of a transport mechanism but rather to a requirement for higher antibiotic concentrations before the second mode of uptake could become operative.

Identification of a second tetracycline-inducible polypeptide encoded by Tn10

“…The mechanism of tetracycline resistance (Tetr) appears to involve an inhibition in the uptake of tetracycline (1,5,6). In addition, there may be an intracellular system that contributes to the resistance (24,33).…”

Bacterial resistance to the tetracyclines.

“…Protonation may promote binding of antibiotic molecules to the surface of the membrane by interaction with anionic residues. These events could represent the initial energy-independent phase of uptake noted by several authors (43,97,98).…”

Antibacterial and Inducer Activities for Tetracycline Resistance by Its Derivatives and Analogues

“…Studies carried out in several laboratories have shown that, unlike other types of bacterial resistance, TC resistance is not due to either the modification of ribosome(s) and of protein synthetic machinery or of enzymatic destruction of the drug (3,8,10). Instead, the TC resistance in naturally occurring resistant strains of gram-positive and gram-negative bacteria is known to be due to a decrease in the permeability of the drug in bacterial cells resulting in the reduction of intracellular concentration of the drug (1)(2)(3)(4).…”

“…In previous papers (4,13), induction of tetracycline (TC) resistance was investigated with a TC resistant strain of Staphylococcus aureus which was isolated from a clinical source. In strains with inducible TC resistance, the mechanism of the resistance has been considered to be a specific decrease of permeability of the bacterial membrane (2,4,7,13). Recent studies by curing experiments and transduction to a rec-recipient revealed that almost all genetic determinants governing TC resistance in staphylococci are located on a plasmid (S. Mitsuhashi Numerous studies on effect of chemical modifications of drugs on their biological activity have been performed before the elucidation of biochemical mechanisms of bacterial resistance.…”