title: Mg2+ homeostasis and avoidance of metal toxicity.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, 660 S. Euclid, Campus Box 8230, St Louis, MO 63110, USA.
authors.forename: Sangpen
authors.initials: S
authors.lastname: Chamnongpol
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D017301:Ca(2+) Mg(2+)-ATPase / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D007501:Iron / Q000633:toxicity; D008274:Magnesium / Q000378:metabolism* / Q000633:toxicity; D016296:Mutagenesis; D009532:Nickel / Q000378:metabolism / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D019779:Salmonella enterica / Q000187:drug effects / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002413:Cations, Divalent; C072716:CorA protein, Salmonella; C061064:PhoP protein, Bacteria; D009532:Nickel; D007501:Iron; D017301:Ca(2+) Mg(2+)-ATPase; D008274:Magnesium; D001205:Ascorbic Acid