Mg2+ homeostasis and avoidance of metal toxicity

Abstract

SummaryBecause 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.