The ins and outs of virulence gene expression: Mg2+ as a regulatory signal

Abstract

The facultative intracellular pathogen Salmonella enterica serovar Typhimurium faces multiple environments during infection, including different cell types as well as extracellular fluids. We propose that Salmonella ascertains its cellular location by assessing the Mg2+ concentration of its milieu. A signal transduction system, PhoP/PhoQ, signals Salmonella its presence in a intracellular (low Mg2+) or extracellular (high Mg2+) environment, thereby promoting transcription of genes required for survival within or entry into host cells. The PhoP/PhoQ system is high in a regulatory hierarchy that controls other signal transduction systems that respond to different host cues, enabling the microorganism to determine its precise tissue and cellular location. BioEssays 20:96–101, 1998. © 1998 John Wiley & Sons, Inc.

Mg 2+ regulates transcription of mgtA in Salmonella Typhimurium via translation of proline codons during synthesis of the MgtL peptide

“…The PhoQP twocomponent system was suggested to activate transcription of mgtA at low extracellular Mg 2+ concentrations (6,9), and the mgtA 5′ LR mRNA has been proposed to function as an Mg 2+ -sensing riboswitch that regulates read-through or Rho-dependent transcription termination at a site upstream of the mgtA structural gene in response to intracellular Mg 2+ (11,15). Subsequently, it was noted that translation of the Pro codon-rich mgtL ORF encoded in the mgtA 5′ LR mRNA is involved in the regulation (12,13).…”

“…One facet of the current model of Salmonella pathogenesis is that the PhoQP system, which is a global regulator of a number of virulence genes, is not active at high Mg 2+ concentrations that are likely found in environments where bacteria are free-living but becomes activated when bacteria infect animal hosts where the concentration of Mg 2+ is presumably low (6). The significance of regulation of pathogenesisrelated genes by physiological concentrations of Mg 2+ is controversial (3).…”

“…Because we used derivatives of the attenuated S. enterica serovar Typhimurium strain LT2 for our work, whereas much of the characterization of the PhoQP regulon has been carried out in the pathogenic strain ATCC 14028s (6,9), the possibility existed that lack of repression of the mgtLA promoter at high Mg 2+ might be a feature of LT2 derivatives. However, we ruled out this possibility by observing that mgtA-lacZ fusion was expressed at similar high levels at 10 mM Mg 2+ in LT2 and ATCC 14028s strains harboring the mgtL (C98T) mutation or deletion of the 5′ LR (Δ9-244) (Fig.…”

“…The PhoQP system regulates directly or indirectly the transcription of 5% of the genes of Salmonella and Escherichia coli, including the phoPQ operon itself and genes involved in virulence, membrane composition, antimicrobial peptide resistance, and acid stress resistance (5). The kinase activity of PhoQ is stimulated by diverse signals, including low concentrations of Mg 2+ (6), acidic pH (7), and a number of antimicrobial peptides (8). Because the cytoplasm of macrophages and phagosomes is acidic and limiting for Mg 2+ , it has been proposed that Salmonella uses the PhoQP system to induce virulence genes needed for growth inside host cells (6,9,10).…”

“…The kinase activity of PhoQ is stimulated by diverse signals, including low concentrations of Mg 2+ (6), acidic pH (7), and a number of antimicrobial peptides (8). Because the cytoplasm of macrophages and phagosomes is acidic and limiting for Mg 2+ , it has been proposed that Salmonella uses the PhoQP system to induce virulence genes needed for growth inside host cells (6,9,10).…”