Signal Transduction Cascade between EvgA/EvgS and PhoP/PhoQ Two-Component Systems of
            <i>Escherichia coli</i>

Eguchi, Yawara; Okada, Tadashi; Minagawa, Shu; Oshima, Taku; Mori, Hirotada; Yamamoto, Kaneyoshi; Ishihama, Akira; Utsumi, Ryutaro

doi:10.1128/jb.186.10.3006-3014.2004

Cited by 69 publications

(54 citation statements)

References 36 publications

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“…The status of the PhoP box is differentiated between a PhoP-regulated gene and an SlyA and PhoP-regulated gene (including pagD-type and pagCtype), and therefore different levels of PhoP are required to antagonize the inhibitory activity of H-NS (14). PhoP is a transcriptional activator required for expression of PhoP-regulated genes carrying a PhoP box that overlaps the -35 region (12,33). This motif in such promoters depends functionally on its orientation, probably because the reverse sequence in this box would change the interaction of PhoP and RNA polymerase, thereby nullifying PhoP-regulated mgtA transcription (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium

Zhao¹,

Weatherspoon²,

Kong

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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We present a molecular mechanism for signal transduction that activates transcription of the SlyA regulon in Salmonella typhimurium. We demonstrate that SlyA mediates transcriptional activation in response to guanosine tetraphosphate, ppGpp, according to the following observations: (i) in vivo transcription of SlyAdependent genes is repressed when ppGpp is absent; this transcription can be restored by overproducing SlyA; (ii) in vivo dimerization and binding of SlyA to the target promoter are facilitated in the presence of ppGpp; and (iii) in vitro SlyA binding to the target promoter is enhanced when ppGpp is supplemented. Thus, ppGpp must be the cytoplasmic component that stimulates SlyA regulatory function by interacting directly with this regulator in Salmonella. This signaling domain, integrated by the PhoP/PhoQ 2-component system that activates slyA transcription by sensing Mg 2؉ , forms feedforward loops that regulate chromosomal loci identified through a motif search over the S. typhimurium genome. Many such loci are divergent operons, each formed by 2 neighboring genes in which transcription of these 2 loci proceeds in opposite directions. Both genes, however, are controlled by PhoP and SlyA through a single shared PhoP box and SlyA box present in their intergenic regions. A substitution in either box sequence causes a simultaneous cessation of transcription of a divergent operon, pagD-pagC, equivalent to the phenotype in a phoP or slyA mutant. We also identified several chromosomal loci that possess pagCtype genes without the cognate pagD-type genes. Therefore, our results provide a molecular basis for the understanding of SlyAdependent phenotypes associated with Salmonella virulence.feedforward loop ͉ ppGpp ͉ SlyA ͉ divergent operon ͉ PhoP/PhoQ system

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Section: Discussionmentioning

confidence: 99%

A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium

Zhao¹,

Weatherspoon²,

Kong

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, transcriptome analysis of an EvgS-activated strain resulted in the induction of many AR genes. In addition to those AR genes, members of a group of PhoP-regulated genes were also induced, indicating activation of another TCS, the PhoQ/PhoP system (8). A further genetic screening assay revealed a 65-amino-acid small membrane protein that was directly induced by EvgA and directly interacted with the sensor PhoQ at the inner membrane (7).…”

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confidence: 99%

Regulation of Acid Resistance by Connectors of Two-Component Signal Transduction Systems in Escherichia coli

et al. 2011

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“…GadE, in particular, serves as the central regulator of the AR2 system. EvgS/EvgA further activates another TCS, the PhoQ/PhoP system, via a small connector protein, SafA (10)(11)(12). Activation of PhoQ/PhoP also contributes to AR in cells at their exponential-growth stage by increasing the cellular RpoS level via another connector, IraM (13,14).…”

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confidence: 99%

Alkali Metals in Addition to Acidic pH Activate the EvgS Histidine Kinase Sensor in Escherichia coli

Eguchi

Utsumi

2014

J Bacteriol

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Two-component signal transduction systems (TCSs) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. The EvgS/EvgA system is a TCS that confers acid resistance to Escherichia coli cells. Activation of the EvgS sensor initiates a cascade of transcription factors, EvgA, YdeO, and GadE, which induce the expression of a large group of acid resistance genes. We searched for signals activating EvgS and found that a high concentration of alkali metals (Na ؉ , K ؉ ) in addition to low pH was essential for the activation. EvgS is a histidine kinase, with a large periplasmic sensor region consisting of two tandem PBPb (bacterial periplasmic solute-binding protein) domains at its N terminus. The periplasmic sensor region of EvgS was necessary for EvgS activation, and Leu152, located within the first PBPb domain, was involved in the activation. Furthermore, chimeras of EvgS and PhoQ histidine kinases suggested that alkali metals were perceived at the periplasmic sensor region, whereas the cytoplasmic linker domain, connecting the transmembrane region and the histidine kinase domain, was required for low-pH perception.

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Signal Transduction Cascade between EvgA/EvgS and PhoP/PhoQ Two-Component Systems of Escherichia coli

Cited by 69 publications

References 36 publications

A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium

A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium

Regulation of Acid Resistance by Connectors of Two-Component Signal Transduction Systems in Escherichia coli

Alkali Metals in Addition to Acidic pH Activate the EvgS Histidine Kinase Sensor in Escherichia coli

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