Enterohemorrhagic<i>Escherichia coli</i>O157:H7 Disrupts Stat1-Mediated Gamma Interferon Signal Transduction in Epithelial Cells

Ceponis, Peter J. M.; McKay, Derek M.; Ching, Joyce C. Y.; Pereira, Perpetual; Sherman, Philip M.

doi:10.1128/iai.71.3.1396-1404.2003

Cited by 41 publications

(70 citation statements)

References 57 publications

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“…It is increasingly evident that even the LEE homologs do not function in an identical fashion in the two pathogens (1,3). For instance, while tyrosine phosphorylation of Tir (Y474) in the epithelial cell is critical for EPEC-induced changes, EHEC Tir mediates host effects in the absence of tyrosine phosphorylation (5).…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function

et al. 2004

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Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are related intestinal pathogens that harbor highly similar pathogenicity islands known as the locus of enterocyte effacement (LEE). Despite their genetic similarity, these two pathogens disrupt epithelial tight junction barrier function with distinct kinetics. EHEC-induced reduction in transepithelial electrical resistance (TER), a measure of barrier function disruption, is significantly slower and more modest in comparison to that induced by EPEC. The variation in bacterial adherence only partially accounted for these differences. The LEE-encoded effector protein EspF has been shown to be critical for EPEC-induced alterations in TER. EspF from both EPEC and EHEC is expressed and secreted upon growth in tissue culture medium. The mutation of EHEC cesF suggested that the optimal expression and secretion of EHEC EspF required its chaperone CesF, as has been shown for EPEC. In contrast to EPEC espF and cesF, mutation of the corresponding EHEC homologs did not dramatically alter the decrease in TER. These differences could possibly be explained by the presence of additional espF-like sequences (designated U-and M-espF, where the letter designations refer to the specific cryptic prophage sequences on the EHEC chromosome closest to the respective genes) in EHEC. Reverse transcription-PCR analyses revealed coordinate regulation of EHEC U-espF and the LEE-encoded espF, with enhanced expression in bacteria grown in Dulbecco-Vogt modified Eagle's medium compared to bacteria grown in Luria broth. Both EHEC espF and U-espF complemented an EPEC espF deletion strain for barrier function alteration. The overexpression of U-espF, but not espF, in wild-type EHEC potentiated the TER response. These studies reveal further similarities and differences in the pathogenesis of EPEC and EHEC.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function

et al. 2004

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“…For instance, EHEC inhibits interferon (IFN)-c-stimulated tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1) in multiple cell lines (Ceponis et al, 2003), which is mediated by a bacterially encoded factor (Jandu et al, 2006). EHEC-mediated disruption of STAT-1 activation is independent of EHEC-derived toxins (Stx-1 and Stx-2), the LEE pathogenicity island, the O157 : H7 plasmid (pO157), and H7 flagellin (Ceponis et al, 2003). Gene knockout mice provide evidence that the IFN-c-Jak1,2-STAT-1 signal transduction cascade is an essential innate immune response required to combat microbial infections (Shtrichman & Samuel, 2001).…”

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confidence: 99%

“…Using bright-field microscopy, viable and non-viable cells were then enumerated, with the number of viable cells calculated as a percentage of the total cell count. At the end of the 6 h infection period, cells were washed once with sterile PBS (pH 7.4) to remove non-adherent bacteria and then stimulated with human recombinant IFN-c (50 ng ml 21 ; R&D Systems) for 30 min at 37 uC in 5 % CO 2 (Ceponis et al, 2003;Jandu et al, 2006 Jandu et al, , 2007. Subsequently, cells were washed three times with ice-cold PBS and collected, using a rubber scraper, into a final 1 ml volume of PBS.…”

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“…To determine whether the benefits of probiotics required epithelial cell contact, cultured epithelia were grown in a 12-well tissue-culture plate fitted with 0.4 mm pore-size Transwell filter membranes (Costar). Bacteria were physically separated from epithelial cells by growing the epithelia in the top chamber of the Transwell, while bacteria were added into the bottom chamber (Ceponis et al, 2003).Bacterial strains and growth conditions. Bacterial strains used in this study included EHEC strain CL56 (serotype O157 : H7), enteropathogenic E. coli (EPEC) strain E2348/69 (serotype O127 : H6) and the non-pathogenic laboratory E. coli strain HB101.…”

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Probiotics prevent enterohaemorrhagic Escherichia coli O157 : H7-mediated inhibition of interferon-γ-induced tyrosine phosphorylation of STAT-1

et al. 2009

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Enterohaemorrhagic Escherichia coli (EHEC) O157 : H7 inhibits interferon (IFN)-c-stimulated tyrosine phosphorylation of signal transducer and activator of transcription (STAT)-1 in epithelial cells. We determined the effects of probiotics on EHEC-mediated disruption of IFN-c-stimulated STAT-1 activation in epithelial cell lines. Confluent Intestine 407, HEp-2 and Caco-2 epithelial cells were pre-treated (3 h) with either probiotics or surface-layer proteins derived from Lactobacillus helveticus R0052 prior to infection with EHEC O157 : H7 strain CL56 (m.o.i. 100 : 1, 6 h, 37 6C in 5 % CO 2 ). Subsequently, cells were washed and stimulated with human recombinant IFN-c (50 ng ml "1 , 0.5 h, 37 6C) followed by whole-cell protein extraction and immunoblotting for tyrosine-phosphorylated STAT-1. Relative to uninfected cells, STAT-1-activation was reduced after EHEC O157 : H7 infection. Pre-incubation with the probiotic L. helveticus R0052 followed by EHEC infection abrogated pathogen-mediated disruption of IFNc-STAT-1 signalling. As determined using Transwell inserts, probiotic-mediated protection was independent of epithelial cell contact. In contrast, pre-incubation with boiled L. helveticus R0052, an equal concentration of viable Lactobacillus rhamnosus R0011, or surface-layer proteins (0.14 mg ml "1 ) did not restore STAT-1 signalling in EHEC-infected cells. The viable probiotic agent L. helveticus R0052 prevented EHEC O157 : H7-mediated subversion of epithelial cell signal transduction responses. INTRODUCTIONOutbreaks of enterohaemorrhagic Escherichia coli (EHEC) serotype O157 : H7 infection occur frequently across the developed world (Serna & Boedeker, 2008). This foodborne enteric pathogen is acquired from contaminated foodstuffs and non-chlorinated drinking water (Karch et al., 2005;Maki, 2006;Rangel et al., 2005). In the severest cases of infection (~10-15 % of cases), the haemolytic uraemic syndrome develops as a systemic complication, leading to patient hospitalization, kidney failure and death (Serna & Boedeker, 2008;Tarr et al., 2005). Renal disease results from bacterial cytotoxin [Shiga-like toxin (Stx)-1 and -2] production in the gut, release into the systemic circulation and damage to vascular endothelial cells in the renal glomerulus (Blackall & Marques, 2004). EHEC pathogenesis is also attributed to intimate bacterial adhesion conferred by the locus of enterocyte effacement (LEE) pathogenicity island, the activity of effector proteins secreted through a type three secretion system (T3SS), and pathogen modulation of host cell signal transduction cascades (Bhavsar et al., 2007;Kaper et al., 2004).EHEC disease pathogenesis includes subversion of epithelial cell signal transduction cascades involved in host innate immune responses to infection (Bhavsar et al., 2007). For instance, EHEC inhibits interferon (IFN)-c-stimulated tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1) in multiple cell lines (Ceponis et al., 2003), which is mediated by a bacterially encoded fac...

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“…EHEC O157:H7 inhibits the signaling of Stat-1 normally activated by interferon-gamma in epithelial cells (Ceponis et al 2003). The effects are dependent on viable organisms binding to the cell surface.…”

Section: Inhibition Of Stat-1 Signalingmentioning

confidence: 99%

Epithelial cell signaling responses to enterohemorrhagic Escherichia coli infection

Ceponis

Riff

Sherman

2005

Mem. Inst. Oswaldo Cruz

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Enterohemorrhagic Escherichia coli, including the serotype O157:H7 that is most commonly identified with human disease, cause both sporadic cases and outbreaks of non-bloody diarrhea and hemorrhagic colitis. In about 10% of infected subjects, the hemolytic uremic syndrome (hemolytic anemic, thrombocytopenia, and acute renal failure) develops, likely as a consequence of systemic spread of bacterial-derived toxins variously referred to as Shiga-like toxin, Shiga toxin, and Verotoxin. Increasing evidence points to a complex interplay between bacterial products -for example, adhesins and toxins -and host signal transduction pathways in mediating responses to infection. Identification of critical signaling pathways could result in the development of novel strategies for intervention to both prevent and treat this microbial infection in humans.Key words: adherence -apoptosis -cytokine -O157:H7 -Shiga-like toxin -Verotoxin Microbial infections are characterized by a stereotypic pattern of host inflammatory responses to the infectious insult (Lawrence et al. 2002). In the intestinal tract, multiple invasive pathogens, including bacteria, parasites and viruses, may induce an enterocolitis in the infected host. Increasingly, evidence indicates that non-invasive gastrointestinal pathogens also are capable of inducing host inflammatory responses by pirating signaling transduction events in infected epithelial cells (Hecht 2001).Escherichia coli O157:H7 infection was first identified in the early 1980's in association with two outbreaks of hemorrhagic colitis in the United States of America. Infection was associated with the ingestion of undercooked hamburger (Thorpe 2004). E. coli O157:H7 has been characterized as a non-invasive enteric pathogen that elaborates phage-encoded toxins variously referred to as Shiga-like toxins, Shiga toxins, and Vero cytotoxins. Subsequent studies showed that multiple E. coli serotypes produce Shiga-like toxins, and that many, but not all, of the various serotypes have been associated with human disease. Isolates associated with human disease are also referred to as enterohemorrhagic E. coli (EHEC) to distinguish them from other serotypes of Shiga-like toxin-producing E. coli that have not been demonstrated to cause disease in man. In addition to the cytotoxins, The environmental reservoir for EHEC is the anorectum of ruminants, including cattle (Naylor et al. 2003). These animals are generally asymptomatic. Moreover, one group of investigators recently provided provocative evidence indicating that carriage of Shiga-like toxin-producing E. coli benefits the ruminant, since toxin binding to cells infected with an oncogenic virus, but not to uninfected cells, leads to programmed cell death of the virus-infected cell (Menge et al. 2004).Fecal contamination of meats, fruits, and vegetables (e.g. non-pasteurized apple cider, radish sprouts), water supplies (including unchlorinated drinking water, swimming pools, and lakes) each have been reported as routes of transmission (Kassenborg et al. 2004...

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EnterohemorrhagicEscherichia coliO157:H7 Disrupts Stat1-Mediated Gamma Interferon Signal Transduction in Epithelial Cells

Cited by 41 publications

References 57 publications

Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function

Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function

Probiotics prevent enterohaemorrhagic Escherichia coli O157 : H7-mediated inhibition of interferon-γ-induced tyrosine phosphorylation of STAT-1

Epithelial cell signaling responses to enterohemorrhagic Escherichia coli infection

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