The CorC proteins MgpA (YoaE) and CorC protect from excess-cation stress and are required for egg white tolerance and virulence in Salmonella

Cation homeostasis is a vital function. In Salmonella , growth in very low Mg ²⁺ induces expression of high-affinity Mg ²⁺ transporters and synthesis of polyamines, organic cations that substitute for Mg ²⁺ . Once Mg ²⁺ levels are re-established, the polyamines must be excreted by PaeA. Otherwise, cells lose viability due to a condition we term excess-cation stress. We sought additional tolerance mechanisms for this stress. We show that CorC and MgpA (YoaE) are essential for survival in stationary phase after Mg ²⁺ starvation. Deletion of corC causes a loss of viability additive with the paeA phenotype. Deletion of mgpA causes a synthetic defect in the corC background. This lethality is suppressed by loss of the inducible Mg ²⁺ transporters, suggesting that the corC mgpA mutant is sensitive to changes in intracellular Mg ²⁺ . CorC and MgpA function independently of PaeA. A paeA mutant is sensitive to externally added polyamine in stationary phase; loss of CorC and MgpA suppressed this sensitivity. Conversely, the corC mgpA mutant, but not the paeA mutant, exhibited sensitivity to high Mg ²⁺ and egg white. The corC mgpA mutant is also attenuated in a mouse model. The corC and mgpA genes are induced in response to increased Mg ²⁺ concentrations. Thus, CorC and MgpA play some interrelated role in cation homeostasis. It is unlikely that these phenotypes are due to absolute levels of cations. Rather, the cell maintains relative concentrations of various cations that likely compete for binding to anionic components. Imbalance of these cations affects some essential function(s), leading to a loss of viability.