Modulation of the regulatory activity of bacterial two-component systems by SlyA

Haowei Song, Wei Kong, Natasha Weatherspoon, Guozheng Qin, William Tyler, John Turk, Roy Curtiss, Yixin Shi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Activation of the transcriptional regulator SlyA by the PhoP/PhoQ two-component system controls intracellular expression of numerous factors influencing Salmonella virulence. By dissecting the SlyA regulon using stable isotope labeling with amino acids in cell culture analysis, we found that SlyA enhances overall transcription of PhoP-activated loci. This amplification of cellular responses to Mg2+ occurs when SlyA binds to the phoPQ promoter thereby activating phoP autoregulation via a positive feedback mechanism. SlyA footprints a DNA region located one helical turn upstream of the PhoP box, which overlaps the H-NS-binding motif required for signal-dependent phoP repression in high Mg2+ conditions. Therefore, binding of SlyA likely antagonizes H-NS and facilitates the interaction of PhoP to its own promoter, subsequently activating the phoPQ operon. Establishment of this regulatory circuit allows SlyA to exert its effect on the PhoP/PhoQ system specifically in Salmonella, which may confer an additional transcriptional regulation. Thus, our results provide a molecular mechanism that determines SlyA-dependent activation of PhoP-regulated genes in modulating Salmonella virulence. Evidence from this study also suggests a function of SlyA as a mediator in signal transduction from the PhoP/PhoQ system to other bacterial two-component systems in Salmonella.

Original languageEnglish (US)
Pages (from-to)28158-28168
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number42
DOIs
StatePublished - Oct 17 2008

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Salmonella
Modulation
Virulence
DNA Footprinting
Chemical activation
Isotope Labeling
Regulon
Signal transduction
Transcription
Operon
Cell culture
Isotopes
Labeling
Transcriptional Activation
Amplification
Signal Transduction
Homeostasis
Cell Culture Techniques
Genes
Feedback

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Modulation of the regulatory activity of bacterial two-component systems by SlyA. / Song, Haowei; Kong, Wei; Weatherspoon, Natasha; Qin, Guozheng; Tyler, William; Turk, John; Curtiss, Roy; Shi, Yixin.

In: Journal of Biological Chemistry, Vol. 283, No. 42, 17.10.2008, p. 28158-28168.

Research output: Contribution to journalArticle

Song, Haowei ; Kong, Wei ; Weatherspoon, Natasha ; Qin, Guozheng ; Tyler, William ; Turk, John ; Curtiss, Roy ; Shi, Yixin. / Modulation of the regulatory activity of bacterial two-component systems by SlyA. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 42. pp. 28158-28168.
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