Repression of
            <i>Escherichia coli</i>
            PhoP-PhoQ Signaling by Acetate Reveals a Regulatory Role for Acetyl Coenzyme A

Lesley, Joseph A.; Waldburger, Carey D.

doi:10.1128/jb.185.8.2563-2570.2003

Cited by 28 publications

(20 citation statements)

References 46 publications

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“…It has been suggested previously that in Erwinia chrysanthemi and Providencia stuartii (42,56) the PhoPQ system may sense chemical signals other than divalent cations. In E. coli, the system has been shown to respond to a mildly acidic pH and acetate in addition to Mg 2ϩ (4,41). In conclusion, the work described in this report showed the central role played by the phoPQ regulon in Photorhabdus virulence in insects.…”

Section: Discussionmentioning

confidence: 53%

The PhoP-PhoQ Two-Component Regulatory System of Photorhabdus luminescens Is Essential for Virulence in Insects

Derzelle¹,

Turlin²,

Duchaud

et al. 2004

J Bacteriol

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Photorhabdus luminescens is a symbiont of entomopathogenic nematodes. Analysis of the genome sequence of this organism revealed a homologue of PhoP-PhoQ, a two-component system associated with virulence in intracellular bacterial pathogens. This organism was shown to respond to the availability of environmental magnesium. A mutant with a knockout mutation in the regulatory component of this system (phoP) had no obvious growth defect. It was, however, more motile and more sensitive to antimicrobial peptides than its wild-type parent. Remarkably, the mutation eliminated virulence in an insect model. No insect mortality was observed after injection of a large number of the phoP bacteria, while very small amounts of parental cells killed insect larvae in less than 48 h. At the molecular level, the PhoPQ system mediated Mg 2؉ -dependent modifications in lipopolysaccharides and controlled a locus (pbgPE) required for incorporation of 4-aminoarabinose into lipid A. Mg 2؉ -regulated gene expression of pbgP1 was absent in the mutant and was restored when phoPQ was complemented in trans. This finding highlights the essential role played by PhoPQ in the virulence of an entomopathogen.

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Section: Discussionmentioning

confidence: 53%

The PhoP-PhoQ Two-Component Regulatory System of Photorhabdus luminescens Is Essential for Virulence in Insects

Derzelle¹,

Turlin²,

Duchaud

et al. 2004

J Bacteriol

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“…A similar signal transduction model between the EvgA/EvgS and PhoP/PhoQ systems may exist in E. coli and involve other factors. In addition to the PhoQ sensor sensing Mg 2ϩ and Ca 2ϩ , PhoQ in E. coli was recently reported to be inactivated by acetate in a sensor domainindependent mechanism (15). Thus, there is a possibility that PhoQ in E. coli may sense stimulants other than Mg 2ϩ and Ca 2ϩ , which may involve the EvgA/EvgS system.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2004

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Transcriptional analysis of a constitutively active mutant of the EvgA/EvgS two-component system of Escherichia coli resulted in enhanced expression of 13 PhoP/PhoQ-regulated genes, crcA, hemL, mgtA, ompT, phoP, phoQ, proP, rstA, rstB, slyB, ybjG, yrbL, and mgrB. This regulatory network between the two systems also occurred as a result of overproduction of the EvgA regulator; however, enhanced transcription of the phoPQ genes did not further activate expression of the PhoP/PhoQ-regulated genes. These results demonstrated signal transduction from the EvgA/EvgS system to the PhoP/PhoQ system in E. coli and also identified the genes that required the two systems for enhanced expression. This is one example of the intricate signal transduction networks that are posited to exist in E. coli.

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“…Identifying the specific signals sensed by the histidine kinase PhoR, whether Mg 2ϩ as in Salmonella (4), phosphate as in Streptomyces (36), acetate as in E. coli (37), or otherwise, is now required to determine under which conditions and toward which aim(s) the production of methyl-branched fatty acids-containing acyltrehaloses is regulated. Several approaches, including promoter fishing and proteomics, have been undertaken by our laboratories to complete our understanding of this important two-component regulator.…”

Section: Discussionmentioning

confidence: 99%

The Virulence-associated Two-component PhoP-PhoR System Controls the Biosynthesis of Polyketide-derived Lipids in Mycobacterium tuberculosis

Gonzalo-Asensio

Maia

Ferrer

et al. 2006

Journal of Biological Chemistry

197

175

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Two-component regulatory signal transduction systems are important elements of the adaptative response of prokaryotes to a variety of environmental stimuli. Disruption of PhoP-PhoR in Mycobacterium tuberculosisdramatically attenuates virulence, implying that this system directly and/or indirectly coordinates the expression of important virulence factors whose identity remains to be established. Interestingly, in knockingout the PhoP-PhoR two-component system in M. tuberculosis Mt103, dramatic changes in the colonial morphology, cording properties, and reactivity of the mutant strain to the basic dye neutral red, all intrinsic properties of tubercle bacilli known to correlate with virulence, were noted. Because deficiencies in the ability of the mutant to form serpentine cords and stain with the dye are likely the results of alterations of its cell envelope composition, we undertook to analyze the lipid content of phoP and phoP-phoR mutants constructed in two different strains of M. tuberculosis. Our results indicate that PhoP coordinately and positively regulates the synthesis of methyl-branched fatty acid-containing acyltrehaloses known to be restricted to pathogenic species of the M. tuberculosis complex, namely diacyltrehaloses, polyacyltrehaloses, and sulfolipids. Evidence is also provided that PhoP but not PhoR is required for the production of these lipids. This work represents an important step toward the functional characterization of PhoP-PhoR and the understanding of complex lipid synthesis in M. tuberculosis.Mycobacterium tuberculosis, the causative agent of tuberculosis in humans, is one of the leading causes of mortality due to a single infectious agent (1). In the tubercle bacillus as in other prokaryotes, two-component signal transduction systems are important elements of the adaptative response to a variety of stimuli (2). So far, of the 11 paired two-component systems, 5 unpaired response regulators and 2 unpaired protein sensors that M. tuberculosis possesses, the two-component system PhoP-PhoR is the one whose disruption was shown to affect the most dramatically the ability of M. tuberculosis to replicate in cellular and animal models (3). Interestingly, PhoP shows high similarity to the PhoP response regulator of Salmonella enterica serovar typhimurium, which senses Mg 2ϩ starvation and controls the expression of at least 40 genes, among which some encoding important virulence determinants (4). Further supporting the concept that PhoP is important for virulence and transmissibility of tubercle bacilli, a multidrug-resistant strain of Mycobacterium bovis (strain B) responsible for large tuberculosis outbreaks in Spain was found to carry an IS6110 insertion in the promoter region of phoP causing a strong up-regulation of the expression of this gene (5). To date, the stimuli sensed by the sensor histidine kinase PhoR and the genes controlled by the DNA-binding response regulator PhoP are not known. The identification of the environmental signals regulating PhoP-PhoR and the characterization of t...

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Repression of Escherichia coli PhoP-PhoQ Signaling by Acetate Reveals a Regulatory Role for Acetyl Coenzyme A

Cited by 28 publications

References 46 publications

The PhoP-PhoQ Two-Component Regulatory System of Photorhabdus luminescens Is Essential for Virulence in Insects

The PhoP-PhoQ Two-Component Regulatory System of Photorhabdus luminescens Is Essential for Virulence in Insects

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

The Virulence-associated Two-component PhoP-PhoR System Controls the Biosynthesis of Polyketide-derived Lipids in Mycobacterium tuberculosis

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