PhoP Can Activate Its Target Genes in a PhoQ-Independent Manner

Abstract

The PhoP/PhoQ two-component system controls the extracellular magnesium depletion response in Salmonella enterica. Previous studies have shown that PhoP is unable to up-regulate its target genes in the absence of PhoQ function. In this work, we demonstrate that PhoP overexpression can substitute for PhoQ-and phosphorylation-dependent activation. Either a high concentration of PhoP or activation via phosphorylation stimulates PhoP self-association.

Signal-dependent Binding of the Response Regulators PhoP and PmrA to Their Target Promoters in Vivo

“…For example, in vitro experiments have shown that unphosphorylated PhoP protein can specifically bind to DNA (10,25) and promote transcription from the mgtA promoter (9). Likewise, overexpression of the PhoP protein at Ͼ10-fold higher levels than those normally produced by the wild-type strain from its promoters allowed transcription of PhoP-regulated genes even in the absence of the sensor protein PhoQ, which is required for PhoP phosphorylation (12).…”

“…Likewise, phospho-PmrA binds more tightly to its target promoters than unphosphorylated PmrA (11). Surprisingly, overexpression of the PhoP protein can reportedly promote gene transcription in a phoQ mutant or when the putative phosphorylation site of the PhoP protein has been mutated (12), suggesting that phosphorylation of the PhoP protein may not be required for binding to its target promoters. To examine the role of low Mg 2ϩ -induced phosphorylation in PhoP-and PmrA-regulated gene expression, we investigated binding of the PhoP and PmrA proteins to their target DNAs in vivo using chromatin immunoprecipitation (ChIP).…”

Phosphorylation of PhoP Protein Plays Direct Regulatory Role in Lipid Biosynthesis of Mycobacterium tuberculosis

“…Furthermore, genetic studies on complementation of 1237⌬phoPR::hyg (a 774-bp fragment of M. tuberculosis genome encompassing part of the phoP and phoR coding sequences was replaced with a hygromycin resistance cassette; see Ref. 5) with phoP alone could restore lipid biosynthesis (5) suggesting that phosphorylation may not be essential for regulation of target genes as has been shown by PhoQ-independent activation of target genes of Salmonella enterica PhoP (20). However, there is evidence that response regulators often get phosphorylated by noncognate kinases belonging to different TCSs (for a review see Ref.…”

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

“…These results indicate that there is no substantial difference in Mg 2+ sensing by the PhoQP systems of the two strains. It has been shown (36) that when synthesized at high levels, unphosphorylated PhoP can activate transcription from some of its target promoters in the absence of the PhoQ sensor kinase and thus independently of sensing of periplasmic Mg 2+ . In our strains, PhoP is produced at wild-type levels, but nevertheless it is able to turn on transcription from the mgtLA promoter in the constitutively ON mutants even at high Mg 2+ concentrations, suggesting that high-level phosphorylation of this protein may not be necessary for the transcriptional activation of this promoter.…”