Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica

Self Cite

110

122

The sigma factor RpoS regulates the expression of many stress response genes and is required for virulence in several bacterial species. We now report that RpoS accumulates when Salmonella enterica serovar Typhimurium is growing logarithmically in media with low Mg 2؉ concentrations. This process requires the twocomponent regulatory system PhoP͞PhoQ, which is specifically activated in low Mg 2؉ . We show that PhoP controls RpoS protein turnover by serving as a transcriptional activator of the iraP (yaiB) gene, which encodes a product that enhances RpoS stability by interacting with RssB, the protein that normally delivers RpoS to the ClpXP protease for degradation. Mutation of the phoP gene rendered Salmonella as sensitive to hydrogen peroxide as an rpoS mutant after growth in low Mg 2؉ . In Escherichia coli, low Mg 2؉ leads to only modest RpoS stabilization, and iraP is not regulated by PhoP͞PhoQ. These findings add the sigma factor RpoS to the regulatory proteins and two-component systems that are elevated in a PhoP͞PhoQ-dependent fashion when Salmonella face low Mg 2؉ environments. Our data also exemplify the critical differences in regulatory circuits that exist between the closely related enteric bacteria Salmonella and E. coli.IraP ͉ magnesium ͉ Escherichia coli

Section: Discussionmentioning

confidence: 99%

“…The sensor protein PhoQ responds to low Mg 2ϩ by promoting phosphorylation of the response regulator PhoP (28)(29)(30)(31), which binds to its target promoters to stimulate transcription of PhoP-activated genes (24,32). The Salmonella PhoP͞PhoQ system controls expression of Ϸ3% of the genome (33).…”

mentioning

confidence: 99%

The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enterica

Latifi²,

Bougdour³

et al. 2006

Self Cite

110

122

“…First, a comparison with previously reported Salmonella PhoP-regulated promoters (Fig. 3A) (23,26) revealed that the sequence of the PhoP-binding motif is similar in Salmonella and Yersinia (Fig. S5).…”

Section: Promoter Architecture Dictates the Ability Of The Salmonellamentioning

confidence: 99%

“…We began by investigating Yersinia's ability to promote transcription of the S. enterica mgtA and ugtL genes, which have no orthologs in Y. pestis and harbor distinct promoter architectures (Fig. 1A) (21)(22)(23). Y. pestis produced fluorescence levels similar to those of S. enterica when transcription of a promoterless gfp gene was driven by the promoter of the mgtA gene (Fig.…”

Section: Differential Ability Of the Yersinia Phop Protein To Expressmentioning

confidence: 99%

Transcription factor function and promoter architecture govern the evolution of bacterial regulons

Pérez

Groisman

2009

Self Cite

Evolutionary changes in ancestral regulatory circuits can bring about phenotypic differences between related organisms. Studies of regulatory circuits in eukaryotes suggest that these modifications result primarily from changes in cis-regulatory elements (as opposed to alterations in the transcription factors that act upon these sequences). It is presently unclear how the evolution of gene regulatory circuits has proceeded in bacteria, given the rampant effects of horizontal gene transfer, which has significantly altered the composition of bacterial regulons. We now demonstrate that the evolution of the regulons governed by the regulatory protein PhoP in the related human pathogens Salmonella enterica and Yersinia pestis has entailed functional changes in the PhoP protein as well as in the architecture of PhoP-dependent promoters. These changes have resulted in orthologous PhoP proteins that differ both in their ability to promote transcription and in their role as virulence regulators. We posit that these changes allow bacterial transcription factors to incorporate newly acquired genes into ancestral regulatory circuits and yet retain control of the core members of a regulon.cis-regulatory elements ͉ horizontal gene transfer ͉ PhoP ͉ Salmonella ͉ Yersinia

“…[The latter genes harbor prototypical PhoP-dependent promoters (13)(14)(15)(16) such as that corresponding to the mgtA gene, which does not require proteins other than PhoP and RNA polymerase for in vitro transcription (ref. 17; J. C. Perez and E.A.G., unpublished data).…”

Section: Pmra-activated Genes Are Induced To Higher Levels Than Thosementioning

confidence: 99%

A connector of two-component regulatory systems promotes signal amplification and persistence of expression

Kato

Mitrophanov²,

Groisman³

2007

Self Cite

Organisms rely on a variety of regulatory architectures to control gene transcription. Whereas the functional characteristics of particular architectures are well understood, the properties of newly discovered regulatory designs cannot be easily predicted. One emerging design depends on small proteins that connect twocomponent regulatory systems, which constitute the dominant form of bacterial signal transduction. These connectors enable one system to respond to the signal perceived by a different system. To understand the functional properties of such connector-mediated architectures, we investigated the pathway controlled by the PhoP-dependent connector protein PmrD of Salmonella enterica and contrasted it to the circuit in which genes are regulated directly by the transcription factor PhoP. The PmrD-mediated pathway displayed both signal amplification and persistence of expression when compared with the direct pathway. Mathematical modeling of the two pathways allowed us to identify critical factors responsible for signal amplification. mathematical modeling ͉ Salmonella ͉ signal transduction ͉ transcriptional regulatory circuit ͉ two-component system