The MgtC virulence factor of salmonella enterica serovar typhimurium activates Na⁺,K⁺-ATPase

The mgtC gene of Salmonella enterica serovar Typhimurium encodes a membrane protein of unknown function that is important for full virulence in the mouse. Since mgtC is part of an operon with mgtB which encodes a Mg²⁺- transporting P-type ATPase, MgtC was hypothesized to function in ion transport, possibly in Mg²⁺ transport. Consequently, MgtC was expressed in Xenopus laevis oocytes, and its effect on ion transport was evaluated using ion selective electrodes. Oocytes expressing MgtC did not exhibit altered currents or membrane potentials in response to changes in extracellular H⁺, Mg²⁺, or Ca²⁺, thus ruling out a previously postulated function as a Mg²⁺/H⁺ antiporter. However, addition of extracellular K⁺ markedly hyperpolarized membrane potential instead of the expected depolarization. Addition of ouabain to block the oocyte Na ⁺,K⁺-ATPase completely prevented hyperpolarization and restored the normal K⁺-induced depolarization response. These results suggested that the Na⁺,K⁺-ATPase was constitutively activated in the presence of MgtC resulting in a membrane potential largely dependent on Na⁺,K⁺-ATPase. Consistent with the involvement of Na⁺,K⁺-ATPase, oocytes expressing MgtC exhibited an increased rate of ⁸⁶Rb⁺ uptake and had increased ietracellular free [K⁺] and decreased free [Na⁺] and ATP. The free concentrations of Mg²⁺ and Ca²⁺ and cytosolic pH were unchanged, although the total intracellelar Ca²⁺ content was slightly elevated. These results suggest that the serovar Typhimurium MgtC protein may be involved in regulating membrane potential but does not directly transport Mg²⁺ or another ion.