Metabolite Reversal of Antibiotic Inhibition, Especially Reversal of Aureomycin Inhibition by Riboflavin

Abstract

An approach to the mechanism of action of antibiotics is to ascertain metabolites which are involved directly in the inhibition of the bacterial cell by a specific antibiotic. A simple means of

Clinical pharmacology of the tetracycline antibiotics

“…One may speculate about the biochemical mechanisms responsible for the remarkable effects of the tetracyclines on nitrogen and riboflavin metabolism in man on the basis of the marked concentration of these drugs within the liver, their chelating properties, and the ability of riboflavin, under certain circumstances, to reverse its antimicrobial activity. 104 CTC has been shown to inhibit oxidative phosphorylation in mitochondria of animal tissues, 105 -107 and, under proper conditions, this can be reversed by Mg++. 107 CTC also inhibits organic nitroreductase in cell-free extracts, 108 and this action is reversed by manganese.…”

The Determination of Chlortetracycline in Tissues I. An Improved Pad‐plate Method

“…Effect of kinds of extractant on the recovery of chlortetracycline from tissues. Such extractants as a 0.57 N hydrochloric acid-acetone solution (9,10,13), a hydrochloric acidacetone solution adjusted to pH 4.2 (1) and an M/10 monobasic potassium phosphate solution (11) have been used for assay of chlortctracycline in tissues. Tomiyama ct a/.…”

Further Studies on Potentiation of Inhibitor Action Through Determination of Reversing Metabolites

“…Reversal by a particular metabolite implies that the inhibitor in question prevents growth by interfering with a biochemical pathway involving that metabolite, e. g., its synthesis, utilization, or penetration (see Cowan and Rowatt, 1958, for general review). The ideal situation, several instances of which have been already described (Foster and Pittillo, 1953b;Pittillo and Foster, 1954), is where the inhibitor blocks the biosynthesis of the metabolite.…”

“…Ribofavin. The high toxicity of riboflavin for E. coli strain B in glucose-salts medium has been discovered (Foster and Pittillo, 1953b). The compound is also toxic for Mllicrococcus pyogenes var.…”