Organisms must maintain physiological levels of Mg2+ because this divalent cation is critical for the stabilization of membranes and ribosomes, the neutralization of nucleic acids, and as a cofactor in a variety of enzymatic reactions. In this review, we describe the mechanisms that bacteria utilize to sense the levels of Mg2+ both outside and inside the cytoplasm. We examine how bacteria achieve Mg2+ homeostasis by adjusting the expression and activity of Mg2+ transporters, and by changing the composition of their cell envelope. We discuss the connections that exist between Mg2+ sensing, Mg2+ transport and bacterial virulence. Additionally, we explore the logic behind the fact that bacterial genomes encode multiple Mg2+ transporters and distinct sensing systems for cytoplasmic and extracytoplasmic Mg2+. These analyses may be applicable to the homeostatic control of other cations.

SUMMARY Bacterial mRNAs often contain leader sequences that respond to specific metabolites or ions by altering expression of the associated downstream protein coding sequences. Here we report that the leader RNA of the Mg2+ transporter gene mgtA of Salmonella enterica, which was previously known to function as a Mg2+-sensing riboswitch, harbors an 18-codon proline-rich open reading frame – termed mgtL – that permits intracellular proline to regulate mgtA expression. Interfering with mgtL translation by genetic, pharmacological or environmental means was observed to increase the mRNA levels from the mgtA coding region. Substitution of the mgtL proline codons by other codons abolished the response to proline and to hyperosmotic stress but not to Mg2+. Our findings show that mRNA leader sequences can consist of complex regulatory elements that utilize different mechanisms to sense separate signals and mediate an appropriate cellular response.

Flagella are multiprotein complexes necessary for swimming and swarming motility. In Salmonella enterica serovar Typhimurium, flagella-mediated motility is repressed by the PhoP/PhoQ regulatory system. We now report that Salmonella can move on 0.3% agarose media in a flagella-independent manner when experiencing the PhoP/PhoQ-inducing signal low Mg 2+ . This motility requires the PhoP-activated mgtA, mgtC, and pagM genes, which specify a Mg 2+ transporter, an inhibitor of Salmonella's own F 1 F o ATPase, and a small protein of unknown function, respectively. The MgtA and MgtC proteins are necessary for pagM expression because pagM mRNA levels were lower in mgtA and mgtC mutants than in wild-type Salmonella, and also because pagM expression from a heterologous promoter rescued motility in mgtA and mgtC mutants. PagM promotes group motility by a surface protein(s), as a pagM-expressing strain conferred motility upon a pagM null mutant, and proteinase K treatment eliminated motility. The pagM gene is rarely found outside subspecies I of S. enterica and often present in nonfunctional allelic forms in organisms lacking the identified motility. Deletion of the pagM gene reduced bacterial replication on 0.3% agarose low Mg 2+ media but not in low Mg 2+ liquid media. Our findings define a form of motility that allows Salmonella to scavenge nutrients and to escape toxic compounds in low Mg 2+ semisolid environments.