Salinomycin and citric acid in combination demonstrate bactericidal activity against Gram-negative bacteria

Abstract

Salinomycin (SAM) is a typical ionophore antibiotic that can selectively inhibit the growth of Gram-positive bacteria. Among the various organic acids tested, citric acid could render cells of Escherichia coli, a Gram-negative bacterium, susceptible to the action of SAM. Either SAM or citric acid alone could only exhibit a static growth inhibitory effect, but their combined actions resulted in the generation of a bactericidal effect with a reduction in viable cells and a sustained increase in extracellular K+. A similar combination effect was observed with monensin and nigericin to a lesser extent, but not with valinomycin. These findings suggest that the stimulatory effect of citric acid on the permeability of the bacterial outer membrane to SAM allows this ionophore to interact directly with the inner membrane and cause irreversible impairment of its ion transport function.