Virulence Gene Regulation in
            <i>Escherichia coli</i>

Mellies, Jay L.; Barron, Alex

doi:10.1128/ecosalplus.8.9.1

Cited by 7 publications

(8 citation statements)

References 307 publications

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“…In addition to encoding the T3SS, the LEE also encodes the bacterial adhesin, intimin, its translocated receptor, Tir, and several T3S chaperones and effector proteins (7,10,19). The regulation of EPEC virulence gene expression involves a complex network of regulators (42). In the present communication, we demonstrate that activation of the Cpx pathway negatively affects EPEC T3S by down regulating the expression of several key components of the translocation apparatus as well as the translocated bacterial receptor Tir.…”

mentioning

confidence: 61%

“…In Yersinia, the expression and secretion of effectors are coordinately regulated (22). Extensive work with EPEC has failed to demonstrate a similar mechanism (11,42).…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, the Cpx pathway may impose its effect on some unknown regulator found in both pathogenic and nonpathogenic E. coli strains. Among the regulators conserved across both strain backgrounds are H-NS, IHF, Fis, BipA, and QseA (35,42). All are global regulators that influence a multitude of cellular processes.…”

Section: Discussionmentioning

confidence: 99%

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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

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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.

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confidence: 61%

“…In Yersinia, the expression and secretion of effectors are coordinately regulated (22). Extensive work with EPEC has failed to demonstrate a similar mechanism (11,42).…”

Section: Discussionmentioning

confidence: 99%

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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

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“…H-NS has been implicated as a transcriptional repressor for a diverse array of genes, particularly those involved in environmental adaptation or virulence, via a preferential interaction with intrinsically curved DNA (reviewed in references 14 and 15). In the case of EHEC and EPEC strains, H-NS plays an important role in the "silencing" of genes located in the different operons of the LEE (LEE1 to -5), and it is responsive to multiple environmental signals and regulatory proteins (29). It has been shown that LEE1, encoding the regulatory protein Ler, is inhibited by H-NS at 27°C and activated at 37°C (50).…”

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confidence: 99%

Ler and H-NS, Regulators Controlling Expression of the Long Polar Fimbriae of Escherichia coli O157:H7

et al. 2007

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Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 colonizes the human intestine and is responsible for diarrheal outbreaks worldwide. Previously we showed that EHEC produces long polar fimbriae (LPF) and that maximum expression is observed during the exponential phase of growth at 37°C and pH 6.5. In this study, we analyzed the roles of several regulators in the expression of LPF using the ␤-galactosidase reporter system, and we found that H-NS functions as a transcriptional silencer while Ler functions as an antisilencer of LPF expression. Interestingly, deletion of the hns and ler genes in EHEC caused constitutive expression of the fusion reporter protein. Semiquantitative reverse transcription (RT)-PCR was also used to analyze LPF expression in the EHEC ler or hns mutant strain. The hns mutant exhibited an increase in lpf mRNA expression, while expression in the ler mutant was decreased, compared to that in the wild-type strain. Using primer extension analysis, we identified two potential transcriptional start sites within the regulatory region of lpf and located consensus hexamers of ؊10 (CAAGAT) and ؊35 (TTCAAA), which are commonly found in 70 -dependent promoters. Further, we determined whether H-NS and Ler interact directly with the lpf promoter region by using purified His-tagged proteins and electrophoretic mobility shift assays. Our data are the first to show direct binding interactions between the H-NS and Ler proteins within the regulatory sequence of the lpf operon. Based on the electrophoretic mobility shift assay, RT-PCR, primer extension, and ␤-galactosidase assay results, we concluded that the E. coli O157:H7 lpf operon possesses a promoter dependent on 70 , that H-NS binds to the regulatory sequence of lpfA and "silences" the transcription of lpf, and that Ler binds to the regulatory sequence and inhibits the action of the H-NS protein.Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a serious food-borne pathogen causing diarrhea that is often bloody and accompanied by severe abdominal cramps and can result in a life-threatening condition known as the hemolyticuremic syndrome (reviewed in reference 33). The organism can be found living in the intestines of healthy cattle, and eating contaminated meat, especially ground beef, has resulted in multiple outbreaks worldwide (23). Recent E. coli O157:H7 outbreaks have drawn attention to food-borne illnesses, and though official sources were saying that the overall number of cases is on the decline in the United States, consumption of produce, particularly leafy vegetables, is becoming increasingly associated with human infections. This alternate source of infection has set up new challenges for the scientific community in trying to identify novel determinants and regulatory mechanisms implicated in the colonization, survival, and/or pathogenic processes (9,10,40).During the infectious process, EHEC adheres to the intestinal epithelium, where it produces Shiga toxins responsible for the hemorrhagic symptoms. Adhesion of E. coli O157:H7 t...

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“…T ranscription factors of pathogenic bacteria can be important virulence determinants, since they control genes that specify toxins, proteins functioning in nutrient acquisition within the hostile host environment, and products that operate by subverting the host innate immunity (1)(2)(3)(4). For example, in Bacillus anthracis, the causative agent of the zoonotic infectious disease, anthrax, the plasmid-borne atxA gene encodes a transcription factor required for virulence, since it is necessary for the activation of genes for toxin and protective capsule production (5,6).…”

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confidence: 99%

Evidence that Oxidative Stress Induces spxA2 Transcription in Bacillus anthracis Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation

et al. 2016

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Bacillus anthracis possesses two paralogs of the transcriptional regulator, Spx. SpxA1 and SpxA2 interact with RNA polymerase (RNAP) to activate the transcription of genes implicated in the prevention and alleviation of oxidative protein damage. The spxA2 gene is highly upregulated in infected macrophages, but how this is achieved is unknown. Previous studies have shown that the spxA2 gene was under negative control by the Rrf2 family repressor protein, SaiR, whose activity is sensitive to oxidative stress. These studies also suggested that spxA2 was under positive autoregulation. In the present study, we show by in vivo and in vitro analyses that spxA2 is under direct autoregulation but is also dependent on the SpxA1 paralogous protein. The deletion of either spxA1 or spxA2 reduced the diamide-inducible expression of an spxA2-lacZ construct. In vitro transcription reactions using purified B. anthracis RNAP showed that SpxA1 and SpxA2 protein stimulates transcription from a DNA fragment containing the spxA2 promoter. Ectopically positioned spxA2-lacZ fusion requires both SpxA1 and SpxA2 for expression, but the requirement for SpxA1 is partially overcome when saiR is deleted. Electrophoretic mobility shift assays showed that SpxA1 and SpxA2 enhance the affinity of RNAP for spxA2 promoter DNA and that this activity is sensitive to reductant. We hypothesize that the previously observed upregulation of spxA2 in the oxidative environment of the macrophage is at least partly due to SpxA1-mediated SaiR repressor inactivation and the positive autoregulation of spxA2 transcription. T ranscription factors of pathogenic bacteria can be important virulence determinants, since they control genes that specify toxins, proteins functioning in nutrient acquisition within the hostile host environment, and products that operate by subverting the host innate immunity (1-4). For example, in Bacillus anthracis, the causative agent of the zoonotic infectious disease, anthrax, the plasmid-borne atxA gene encodes a transcription factor required for virulence, since it is necessary for the activation of genes for toxin and protective capsule production (5, 6). Other Grampositive bacteria possess genes encoding one or more forms of the ArsC (arsenate reductase) family protein, Spx, which is an RNA polymerase (RNAP)-binding protein directing the expression of large regulons that include genes necessary for pathogenesis (7-11). Studies of streptococci, Listeria monocytogenes, Staphylococcus aureus, and Enterococcus spp. have demonstrated the requirement for Spx proteins for virulence and viability (7,8,(12)(13)(14)(15). IMPORTANCE Regulators of transcription initiationSpx was detected in studies of B. subtilis, in which it is encoded by a gene that is under complex transcriptional control involving four RNAP forms and two repressors (16)(17)(18)(19). The complex control of spx transcription operates in response to various stress conditions, such as oxidative and cell envelope stress. Spx protein levels increase under conditions caus...

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Virulence Gene Regulation in Escherichia coli

Cited by 7 publications

References 307 publications

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

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

Ler and H-NS, Regulators Controlling Expression of the Long Polar Fimbriae of Escherichia coli O157:H7

Evidence that Oxidative Stress Induces spxA2 Transcription in Bacillus anthracis Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation

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