Energetic basis of cadmium toxicity in Staphylococcus aureus

Abstract

In washed cells of cadmium-sensitive Staphylococcus aureus 17810S oxidizing glutamate, initial Cd2+ influx via the Mn2+ porter down membrane potential (delta psi) was fast due to involvement of energy generated by two proton pumps--the respiratory chain and the ATP synthetase complex working in the hydrolytic direction. Such an unusual energy drain for rapid initial Cd2+ influx is suggested to be due to a series of toxic events elicited by Cd2+ accumulation down delta psi generated via the redox proton pump: (i) strong inhibition of glutamate oxidation accompanied by a decrease of electrochemical proton gradient (delta mu H+) formation via the respiratory chain, (ii) automatic reversal of ATP synthetase from biosynthetic to hydrolytic mode, which was monitored by a decrease of delta mu (H+)-dependent ATP synthesis, (iii) acceleration of the initial Cd2+ influx down delta psi generated by the reversed ATP synthetase, the alternative proton pump hydrolyzing endogenous ATP. The primary, cadmium-sensitive targets in strain 17810S seem to be dithiols located in the cytoplasmic glutamate oxidizing system, prior to the membrane-embedded NADH oxidation system. Inhibition by Cd2+ of delta mu (H+)-dependent ATP synthesis and of pH gradient (delta pH)-linked [14C]glutamate transport is a secondary effect due to cadmium-mediated inhibition of delta mu H+ generation at the cytoplasmic level. In washed cells of cadmium-resistant S. aureus 17810R oxidizing glutamate, Cd2+ accumulation was prevented due to activity of the plasmid-coded Cd2+ efflux system. Consequently, delta mu (H+)-producing and -requiring processes were not affected by Cd2+.