Decrease in Accumulation of Macrolide Antibiotics as a Mechanism of Resistance in Staphylococcus aureus

Abstract

A marked difference of levels of accumulation of macrolicle antibiotics (Mac) was found between Mac-sensitive (E642-1 and 209P) and Mac-resistant (MS642, MS57, U9, and 606) strains of Staphylococcus aureus by means of qualitative and quantitative bioassay methods. Though the levels of accumulation of the antibiotics in cells of Mac-resistant strains were only one-tenth that of the Mac-sensitives, satisfactory evidence for a relationship between the accumulation of the antibiotics and the degree of sensitivity to those drugs was established in a physiological sense from a kinetic measurement of K_s and v in the accumulation reaction of the antibiotics in the cells. The experiments with tritiated erythromycin or josamycin also support these results. It is suspected, by estimation of the accumulation in heated or UV-irradiated cells, that levels of accumulation of the antibiotics in cells of S. aureus could be reflected by a binding affinity of their ribosomes for these antibiotics. There was no system for inactivating the antibiotics seen in the cells of the Mac-resistants, i. e., MS642, 606, and U9.