Mg2+ homeostasis and avoidance of metal toxicity

Because Mg2+ is required for a wide variety of cellular functions, its intracellular levels must be tightly regulated. In the Gram-negative bacterium Salmonella enterica, three transporters mediate Mg2+ uptake: the P-type ATPases MgtA and MgtB, whose expression is transcriptionally induced in low Mg2+ by the Mg2+-regulated PhoP/PhoQ two-component system; and CorA, whose transcription is regulated neither by the levels of Mg2+ nor by the PhoP/PhoQ system. We now report that mutants defective in phoP or in both mgtA and mgtB are hypersensitive to oxidative stress-dependent Fe (II)-mediated killing. These mutants display increased iron accumulation and heightened Ni2+ uptake. Inactivation of the corA gene restored Fe(II) resistance to the phoP mutant and eliminated uptake of Ni2+. Neither corA transcription nor CorA protein levels were altered in the phoP mutant, suggesting that CorA alters its activity in response to the presence of PhoP-regulated determinants. Downregulation of CorA activity in low Mg2+ environments may enable Salmonella to avoid the uncontrolled influx of toxic metals.