Co-regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ

William Wiley Navarre, Thomas A. Halsey, Don Walthers, Jonathan Frye, Michael McClelland, Jennifer L. Potter, Linda Kenney, John S. Gunn, Ferric C. Fang, Stephen J. Libby

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Analysis of the transcriptome of slyA mutant Salmonella enterica serovar Typhimurium revealed that many SlyA-dependent genes, including pagC, pagD, ugtL, mig-14, virK, phoN, pgtE, pipB2, sopD2, pagJ and pagK, are also controlled by the PhoP/PhoQ regulatory system. Many SlyA- and PhoP/PhoQ-co-regulated genes have functions associated with the bacterial envelope, and some have been directly implicated in virulence and resistance to antimicrobial peptides. Purified His-tagged SlyA binds to the pagC and mig-14 promoters in regions homologous to a previously proposed 'SlyA-box'. The pagC promoter lacks a consensus PhoP binding site and does not bind PhoP in vitro, suggesting that the effect of PhoP on pagC transcription is indirect. Stimulation of pagC expression by PhoP requires SlyA. Levels of SlyA protein and mRNA are not significantly changed under low-magnesium PhoP-inducing conditions in which pagC expression is profoundly elevated, however, indicating that the PhoP/PhoQ system does not activate pagC expression by altering SlyA protein concentration. Models are proposed in which PhoP may control SlyA activity via a soluble ligand or SlyA may function as an anti-repressor to allow PhoP activation. The absence of almost all SlyA-activated genes from the Escherichia coli K12 genome suggests that the functional linkage between the SlyA and PhoP/PhoQ regulatory systems arose as Salmonella evolved its distinctive pathogenic lifestyle.

Original languageEnglish (US)
Pages (from-to)492-508
Number of pages17
JournalMolecular Microbiology
Volume56
Issue number2
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

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Salmonella enterica
Virulence
Peptides
Genes
Escherichia coli K12
Gene Expression Profiling
Genetic Promoter Regions
Salmonella
Magnesium
Life Style
Consensus
Proteins
Binding Sites
Genome
Ligands
Messenger RNA

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Co-regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ. / Navarre, William Wiley; Halsey, Thomas A.; Walthers, Don; Frye, Jonathan; McClelland, Michael; Potter, Jennifer L.; Kenney, Linda; Gunn, John S.; Fang, Ferric C.; Libby, Stephen J.

In: Molecular Microbiology, Vol. 56, No. 2, 01.04.2005, p. 492-508.

Research output: Contribution to journalArticle

Navarre, WW, Halsey, TA, Walthers, D, Frye, J, McClelland, M, Potter, JL, Kenney, L, Gunn, JS, Fang, FC & Libby, SJ 2005, 'Co-regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ', Molecular Microbiology, vol. 56, no. 2, pp. 492-508. https://doi.org/10.1111/j.1365-2958.2005.04553.x
Navarre, William Wiley ; Halsey, Thomas A. ; Walthers, Don ; Frye, Jonathan ; McClelland, Michael ; Potter, Jennifer L. ; Kenney, Linda ; Gunn, John S. ; Fang, Ferric C. ; Libby, Stephen J. / Co-regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ. In: Molecular Microbiology. 2005 ; Vol. 56, No. 2. pp. 492-508.
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