Role of the Two-Component Regulator CpxAR in the Virulence of
            <i>Salmonella enterica</i>
            Serotype Typhimurium

Humphreys, Sue; Rowley, Gary; Stevenson, Andrew; Anjum, Muna F.; Woodward, Martin J.; Gilbert, S. J.; Kormanec, Ján; Roberts, Mark

doi:10.1128/iai.72.8.4654-4661.2004

Cited by 111 publications

(117 citation statements)

References 45 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…The CpxR response regulator has been shown to be involved in the pathogenesis of Salmonella enterica, Shigella sonnei, enteropathogenic E. coli, and Yersinia sp., and in most cases its involvement was related to contact with eukaryotic cells (7,8,25,40,41). The PmrA response regulator has been shown to be involved in the virulence of S. enterica, Pseudomonas aeruginosa, and Francisella sp., and its involvement was mainly related to its relationship with the PhoP response regulator and resistance to antimicrobial peptides (13,33,35,55).…”

Section: Discussionmentioning

confidence: 99%

The Response Regulator CpxR Directly Regulates Expression of SeveralLegionella pneumophila icm/dotComponents as Well as New Translocated Substrates

2008

View full text Add to dashboard Cite

Legionella pneumophila has been shown to utilize the icm/dot type IV secretion system for pathogenesis. This system was shown to be composed of icm/dot complex components and accessory proteins, as well as a large number of translocated substrates. Bioinformatic analysis of the regulatory regions of all the genes revealed that several icm/dot genes, as well as two genes encoding icm/dot translocated substrates, contain the conserved CpxR regulatory element, a regulator that has been shown previously to control the expression of the icmR gene. An experimental analysis, which included a comparison of gene expression in a L. pneumophila wild-type strain and gene expression in a cpxR deletion mutant, construction of mutants with mutations in the CpxR conserved regulatory elements, controlled expression studies, and mobility shift assays, demonstrated the direct relationship between the CpxR regulator and the expression of the genes. Furthermore, genomic analysis identified nine additional genes that contain a putative CpxR regulatory element; five of these genes (two legA genes and three ceg genes) were suggested previously to be putative icm/dot translocated substrates. The three ceg genes identified, which were shown previously to contain a putative PmrA regulatory element, were found here to be regulated by both CpxR and PmrA. The other six genes (two legA genes and four new genes products were found to be regulated by CpxR. Moreover, using the CyaA translocation assay, these nine gene products were found to be translocated into host cells in an Icm/Dot-dependent manner. Our results establish that the CpxR regulator is a fundamental regulator of the icm/dot type IV secretion system in L. pneumophila.

show abstract

Section: Discussionmentioning

confidence: 99%

The Response Regulator CpxR Directly Regulates Expression of SeveralLegionella pneumophila icm/dotComponents as Well as New Translocated Substrates

2008

View full text Add to dashboard Cite

show abstract

“…Our results agree with and shed light on previous studies of the Cpx response in other pathogens. For example, the interruption of cpxR in Salmonella enterica serovar Typhimurium and Yersinia enterocolitica had no observable effect on virulence in an animal model (27,28). Alternatively, CpxRϳP has been shown to negatively regulate P pilus expression in uropathogenic E. coli (26).…”

Section: Discussionmentioning

confidence: 99%

“…Elegant work with uropathogenic E. coli demonstrated that CpxRϳP binds to a region controlling pap phase variation and inhibits P pilus expression in vivo (26,29). In Salmonella enterica serovar Typhimurium, a cpxA mutant decreases expression of a major regulator of invasion genes, HilA (46), and exhibits a diminished ability to attach to and invade eukaryotic cells (28). Lastly, a CpxR homologue positively regulates transcription of the icm-dot type IV secretion system in Legionella pneumophila (23).…”

mentioning

confidence: 99%

Activation of the Cpx Envelope Stress Response Down-Regulates Expression of Several Locus of Enterocyte Effacement-Encoded Genes in Enteropathogenic Escherichia coli

et al. 2008

View full text Add to dashboard Cite

The Cpx two-component system regulates an extracytoplasmic stress response that functions to rid the envelope of misfolded and mislocalized proteins that may interfere with normal cellular processes. The Cpx pathway is also involved in pathogenesis. This study investigated the role of the Cpx response in enteropathogenic Escherichia coli (EPEC) type III secretion (T3S). It was determined that a functional Cpx pathway is not required for T3S but that pathway activation inhibits secretion by reducing the cellular pools of T3S substrates. The EPEC T3S system structural components, as well as a number of its substrates, are encoded on the locus of enterocyte effacement (LEE) pathogenicity island. Transcriptional fusions to the five major operons of the LEE were constructed and examined under Cpx pathway-activating conditions. Induction of the Cpx response caused a decrease in the transcription of several LEE operons, with the most pronounced effect on LEE4 and LEE5. Collectively, these two operons encode components of the T3S translocation apparatus, the bacterial adhesin intimin, and the translocated bacterial receptor Tir. These data show for the first time that activation of the Cpx envelope stress response in EPEC inhibits T3S of both translocators and effectors, likely through down regulation of LEE transcription. Coupled with recent findings, our results suggest that Cpx-mediated down regulation of virulence is a conserved theme in a number of bacterial pathogens.

show abstract

“…Each response triggers a signaling cascade that leads to the regulation of factors needed to combat envelope damage or to respond to the stress (5). Some envelope stress response signaling has been linked to virulence in Gram-negative bacteria (7,8). For instance, the RcsBC signaling system enhances the locus of enterocyte effacement (LEE) and the adherence phenotype of the STEC O157:H7 isolate TW14359, the isolate responsible for a 2006 outbreak in the United States (8).…”

mentioning

confidence: 99%

“…For instance, the RcsBC signaling system enhances the locus of enterocyte effacement (LEE) and the adherence phenotype of the STEC O157:H7 isolate TW14359, the isolate responsible for a 2006 outbreak in the United States (8). CpxAR is involved in bacterial adhesion (6,7) and is activated during prophage induction in E. coli (9). Finally, BaeSR, which mediates increased resistance to toxic compounds (10), is related to envelope biogenesis (10) and could regulate the expression of surface elements (10).…”

mentioning

confidence: 99%

BaeSR, Involved in Envelope Stress Response, Protects against Lysogenic Conversion by Shiga Toxin 2-Encoding Phages

et al. 2015

View full text Add to dashboard Cite

Infection and lysogenic conversion with Shiga toxin-encoding bacteriophages (Stx phages) drive the emergence of new Shiga toxin-producing Escherichia coli strains. Phage attachment to the bacterial surface is the first stage of phage infection. Envelope perturbation causes activation of envelope stress responses in bacterial cells. Although many external factors are known to activate envelope stress responses, the role of these responses in the phage-bacterium interaction remains unexplored. Here, we investigate the link between three envelope signaling systems in E. coli (RcsBC, CpxAR, and BaeSR) and Stx2 phage infection by determining the success of bacterial lysogenic conversion. For this purpose, E. coli DH5␣ wild-type (WT) and mutant strains lacking RcsBC, CpxAR, or BaeSR signaling systems were incubated with a recombinant Stx2 phage (933W). Notably, the number of lysogens obtained with the BaeSR mutant was 5 log 10 units higher than with the WT, and the same differences were observed when using 7 different Stx2 phages. To assess whether the membrane receptor used by Stx phages, BamA, was involved in the differences observed, bamA gene expression was monitored by reverse transcription-quantitative PCR (RT-qPCR) in all host strains. A 4-fold-higher bamA expression level was observed in the BaeSR mutant than in the WT strain, suggesting that differential expression of the receptor used by Stx phages accounted for the increase in the number of lysogenization events. Establishing the link between the role of stress responses and phage infection has important implications for understanding the factors affecting lysogenic conversion, which drives the emergence of new pathogenic clones.T emperate phages are responsible for the conversion of nonpathogenic strains of bacteria to pathogenic strains by transduction of virulence genes (1). Well-known examples are Shiga toxin (Stx) phages, which carry the genes for Shiga toxin (stx). Stx phages can cause the conversion of Escherichia coli and bacteria of other genera to Shiga toxin-producing E. coli (STEC) and other Shiga-toxigenic pathogens (2). A recent example is the STEC outbreak in Germany in May 2011, where an enteroaggregative E. coli O104:H4 strain incorporated an Stx2 phage (3, 4). Because the lysogeny of E. coli by Stx phages has relevant implications for their pathogenicity, a better understanding of the molecular mechanisms underlying phage-host interaction is a challenge for researchers and could help in designing strategies to avoid lysogenization by Stx phages.The first step in phage infection is attachment to the specific receptor on the bacterial surface. The maintenance, adaptation, and protection of the bacterial envelope are essential for bacteria. Stresses that damage and alter the bacterial envelope can lead to activation of stress responses in bacteria by means of various phosphorelay signaling systems (5). In E. coli, five different envelope stress responses have been identified: BaeSR, CpxAR, RcsBC, Psp, and E (5, 6). Each response triggers a si...

show abstract

Role of the Two-Component Regulator CpxAR in the Virulence of Salmonella enterica Serotype Typhimurium

Cited by 111 publications

References 45 publications

The Response Regulator CpxR Directly Regulates Expression of SeveralLegionella pneumophila icm/dotComponents as Well as New Translocated Substrates

The Response Regulator CpxR Directly Regulates Expression of SeveralLegionella pneumophila icm/dotComponents as Well as New Translocated Substrates

Activation of the Cpx Envelope Stress Response Down-Regulates Expression of Several Locus of Enterocyte Effacement-Encoded Genes in Enteropathogenic Escherichia coli

BaeSR, Involved in Envelope Stress Response, Protects against Lysogenic Conversion by Shiga Toxin 2-Encoding Phages

Contact Info

Product

Resources

About