Diagnosis of Enteropathogenic Escherichia Coli

Knutton, Stuart; Shaw, Robert K.; McNeish, A S; Philips, Alan D.; Price, E. Margaret; Watson, Peter J.

doi:10.1016/s0140-6736(89)90402-9

Cited by 12 publications

(10 citation statements)

References 7 publications

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“…EPEC is closely related to enterohemmorhagic E. coli (EHEC), which causes "raw hamburger" disease, a condition comprising bloody diarrhea and hemorrhagic colitis, which can lead to hemolytic uremic syndrome and death (Riley et al, 1983). A hallmark feature of EPEC infections is the formation of attaching and effacing lesions on the host intestinal epithelia cells (Knutton et al, 1989). These lesions comprise a loss of intestinal microvilli and the formation of an actin-filled membranous pedestal that protrudes beneath the adherent bacterium.…”

Section: Introductionmentioning

confidence: 99%

EnteropathogenicEscherichia coliUse Redundant Tyrosine Kinases to Form Actin Pedestals

Swimm

Bommarius

et al. 2004

MBoC

112

126

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Enteropathogenic Escherichia coli (EPEC) are deadly contaminants in water and food and induce protrusion of actin-rich membrane pedestals beneath themselves upon attachment to intestinal epithelia. EPEC then causes intestinal inflammation, diarrhea, and, among children, death. Here, we show that EPEC uses multiple tyrosine kinases for formation of pedestals, each of which is sufficient but not necessary. In particular, we show that Abl and Arg, members of the Abl family of tyrosine kinases, localize and are activated in pedestals. We also show that pyrido[2,3-d]pyrimidine (PD) compounds, which inhibit Abl, Arg, and related kinases, block pedestal formation. Finally, we show that Abl and Arg are sufficient for pedestal formation in the absence of other tyrosine kinase activity, but they are not necessary. Our results suggest that additional kinases that are sensitive to inhibition by PD also can suffice. Together, these results suggest that EPEC has evolved a mechanism to use any of several functionally redundant tyrosine kinases during pathogenesis, perhaps facilitating its capacity to infect different cell types. Moreover, PD compounds are being developed to treat cancers caused by dysregulated Abl. Our results raise the possibility that PD may be useful in treating EPEC infections, and because PD affects host and not bacterium, selecting resistant strains may be far less likely than with conventional antibiotics. INTRODUCTIONPathogenic Escherichia coli are a significant public health concern. In developing countries, enteropathogenic E. coli (EPEC) contaminates the water supply and causes infantile diarrhea (Goosney et al., 2000). The resulting dehydration contributes to as many as 1 million infant deaths per year (Mead et al., 1999). EPEC is closely related to enterohemmorhagic E. coli (EHEC), which causes "raw hamburger" disease, a condition comprising bloody diarrhea and hemorrhagic colitis, which can lead to hemolytic uremic syndrome and death (Riley et al., 1983). A hallmark feature of EPEC infections is the formation of attaching and effacing lesions on the host intestinal epithelia cells (Knutton et al., 1989). These lesions comprise a loss of intestinal microvilli and the formation of an actin-filled membranous pedestal that protrudes beneath the adherent bacterium. Pedestal formation is highly correlated with development of disease, and mutations in bacterial virulence factors associated with pedestal formation render the bacteria avirulent (Rosenshine et al., 1992;Foubister et al., 1994).To form pedestals, EPEC initially attach loosely to epithelial cells through an adhesin (Frankel et al., 1996;Sinclair and O'Brien, 2002) and express several proteins associated with virulence, including a type III secretion apparatus (Jarvis et al., 1995) and a bacterial outer membrane protein called intimin (Donnenberg et al., 1993). The type III secretion system facilitates translocation of virulence factors into the host cytoplasm and plasma membrane (Goosney et al., 2000). One such factor, called translocated in...

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Section: Introductionmentioning

confidence: 99%

EnteropathogenicEscherichia coliUse Redundant Tyrosine Kinases to Form Actin Pedestals

Swimm

Bommarius

et al. 2004

MBoC

112

126

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“…Morphological studies on both in vivo and in vitro infection systems have identified two distinguishable stages of adherence by EPEC. The first, localized adherence (2,3), is mediated by type IV fimbriae called bundle-forming pili (4). Subsequently there is an alteration of the host cytoskeletal structure, including effacement of the surface microvilli, followed by the appearance of a pedestal-like structure upon which external bacteria are localized (2,3,5).…”

mentioning

confidence: 99%

“…The first, localized adherence (2,3), is mediated by type IV fimbriae called bundle-forming pili (4). Subsequently there is an alteration of the host cytoskeletal structure, including effacement of the surface microvilli, followed by the appearance of a pedestal-like structure upon which external bacteria are localized (2,3,5). Intimate association with epithelial cells requires a bacterial outer membrane protein, intimin, encoded by eaeA (6,7).…”

mentioning

confidence: 99%

Protein secretion by enteropathogenic Escherichia coli is essential for transducing signals to epithelial cells.

Kenny

Finlay

1995

Proc. Natl. Acad. Sci. U.S.A.

228

216

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Enteropathogenic Escherichia coli (EPEC), a major cause of pediatric diarrhea, adheres to epithelial cells and activates host cell signal transduction pathways. We have identified five proteins that are secreted by EPEC and show that this secretion process is critical for triggering signal transduction events in epithelial cells. Protein secretion occurs via two pathways: one secretes a 110-kDa protein and the other mediates export of the four remaining proteins. Secretion of all five proteins was regulated by temperature and the perA locus, two factors which regulate expression of other known EPEC virulence factors. Amino-terminal sequence analysis of the secreted polypeptides identified one protein (37 kDa) as the product ofthe eaeB gene, a genetic locus previously shown to be necessary for signal transduction. A second protein (39 kDa) showed significant homology with glyceraldehyde-3-phosphate dehydrogenase, while the other three proteins (110, 40, and 25 kDa) were unique. The secreted proteins associated with epithelial cells, and EaeB became resistant to protease digestion upon association, suggesting that intimate interactions are required for transducing signals.

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“…EPEC initially adheres loosely to the intestinal epithelium and then consolidates its attachment through more intimate adhesion, causing characteristic attaching and effacing lesions (21,22,40). These interactions result in changes in the host cell plasma membrane architecture and cytoskeletal network, as well as the induction of complex signaling pathways (32, 37).…”

mentioning

confidence: 99%

Enteropathogenic Escherichia coli Infection Triggers Host Phospholipid Metabolism Perturbations

Lau

Smith

et al. 2004

Infect Immun

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Enteropathogenic Escherichia coli (EPEC) specifically recognizes phosphatidylethanolamine (PE) on the outer leaflet of host epithelial cells. EPEC also induces apoptosis in epithelial cells, which results in increased levels of outer leaflet PE and increased bacterial binding. Consequently, it is of interest to investigate whether EPEC infection perturbs host cell phospholipid metabolism and whether the changes play a role in the apoptotic signaling. Our findings indicate that EPEC infection results in a significant increase in the epithelial cell PE level and a corresponding decrease in the phosphatidylcholine (PC) level. PE synthesis via both the de novo pathway and the serine decarboxylation pathway was enhanced, and de novo synthesis of phosphatidylcholine via CDP-choline was reduced. The changes were transitory, and the maximum change was noted after 4 to 5 h of infection. Addition of exogenous PC or CDP-choline to epithelial cells prior to infection abrogated EPEC-induced apoptosis, suggesting that EPEC infection inhibits the CTP-phosphocholine cytidylyltransferase step in PC synthesis, which is reportedly inhibited during nonmicrobially induced apoptosis. On the other hand, incorporation of exogenous PE by the host cells enhanced EPEC-induced apoptosis and necrosis without increasing bacterial adhesion. This is the first report that pathogen-induced apoptosis is associated with significant changes in PE and PC metabolism, and the results suggest that EPEC adhesion to a host membrane phospholipid plays a role in disruption of host phospholipid metabolism.Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen which causes severe infantile diarrhea and is responsible for up to one million deaths annually. EPEC initially adheres loosely to the intestinal epithelium and then consolidates its attachment through more intimate adhesion, causing characteristic attaching and effacing lesions (21,22,40). These interactions result in changes in the host cell plasma membrane architecture and cytoskeletal network, as well as the induction of complex signaling pathways (32, 37).The plasma membrane phospholipid phosphatidylethanolamine (PE) has been identified as a receptor candidate for several pathogens, including EPEC (5,13,38,42). EPEC recognizes PE in a specific and dose-dependent manner in both solid-phase and liposomal assays (5). It binds PE from human epithelial cells extracts, and bacterial adhesion to human epithelial cells can be inhibited with anti-PE (5).Epithelial cell membranes contain considerable PE, and although the majority of it appears on the inner leaflets, up to 30% is presented on the outer leaflets of healthy cells (49) and even more is presented on the outer leaflets of dying cells (4, 23). Bacterial binding of host outer leaflet PE may lead to the sequestration of outer leaflet PE, which could disrupt host cell PE metabolism and possibly the metabolism of other phospholipids.Disruption of phospholipid metabolism in the host cell, particularly metabolism of phosphatidylcholine ...

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Diagnosis of Enteropathogenic Escherichia Coli

Cited by 12 publications

References 7 publications

EnteropathogenicEscherichia coliUse Redundant Tyrosine Kinases to Form Actin Pedestals

EnteropathogenicEscherichia coliUse Redundant Tyrosine Kinases to Form Actin Pedestals

Protein secretion by enteropathogenic Escherichia coli is essential for transducing signals to epithelial cells.

Enteropathogenic Escherichia coli Infection Triggers Host Phospholipid Metabolism Perturbations

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