Caspases-3, -8, and -9 are required for induction of epithelial cell apoptosis by enteropathogenic E. coli but are dispensable for increased paracellular permeability

Flynn, Andrew N.; Buret, André G.

doi:10.1016/j.micpath.2007.10.007

Cited by 26 publications

(26 citation statements)

References 32 publications

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“…TJ organization in fully differentiated T84 cells is not affected by the tEPEC T3SS effector NleE activating Erk1/2 MAPK and NF-B (694). The tEPEC EspF-induced increase in paracellular permeability and ZO-1 delocalization in fully differentiated Caco-2 cells does not relate to the tEPEC EspF-induced caspase 3, 8, and 9 cleavage (695,696).…”

Section: Structural and Functional Injuries At The Junctional Domainmentioning

confidence: 77%

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Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses.

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Section: Structural and Functional Injuries At The Junctional Domainmentioning

confidence: 77%

“…In contrast, the tEPEC OMPs upregulate iNOS, induce nitrite production, and activate NF-B and MAPKs in fully differentiated Caco-2 cells (779). Moreover, tEPEC induces caspase-dependent host cell death in fully differentiated Caco-2 and T84 cells (695,780).…”

Section: Host Cellular Defense Responsesmentioning

confidence: 96%

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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“…While several E. coli serotypes (1,4,9,15) and toxins (3,19) have been shown to induce apoptosis of epithelial cells, the extent to which ETEC damages host cells is unclear. The prototypic ETEC isolate H10407 was cytotoxic to but failed to induce apoptosis in the macrophage cell line J774 (as measured by DNA fragmentation) (24).…”

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confidence: 99%

EnterotoxigenicEscherichia coliModulates Host Intestinal Cell Membrane Asymmetry and Metabolic Activity

et al. 2009

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Enterotoxigenic Escherichia coli (ETEC) is a common cause of travelers' and postweaning diarrhea in humans and swine, respectively. The extent to which ETEC damages host cells is unclear. Experiments are presented that probe the ability of porcine ETEC isolates to induce apoptosis and cell death in porcine intestinal epithelial cells. Quantification of host phosphatidylserine exposure following ETEC infection suggested that ETEC induced changes in plasma membrane asymmetry, independent of the expression of the heat-labile enterotoxin. Significant host cell death was not observed. ETEC infection also caused a drastic inhibition of host esterase activity, as measured by calcein fluorescence. While ETEC infection resulted in activation of host caspase 3, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling of DNA double-strand breakage, indicative of late stages of apoptosis, was not observed. Camptothecin-induced apoptosis markedly increased subsequent ETEC adherence. Transfer of cell-free supernatants from apoptotic cells to bacterial inocula prior to infection of naïve cells increased the transcriptional activity of the regulatory region upstream of the K88ac operon and promoted subsequent adherence to host cells.Enterotoxigenic Escherichia coli (ETEC) causes childhood mortality and travelers' diarrhea in humans (36) and postweaning diarrhea in pigs (32). ETEC adherence to intestinal cells is mediated by proteinaceous, species-specific colonization factors (25). ETEC induces water and electrolyte loss from the intestine due to the activities of several enterotoxins, including the heat-labile enterotoxin (LT), the heat-stable toxins (ST), and the enteroaggregative E. coli heat-stable enterotoxin 1 (32).Bacterial pathogens often induce host cell apoptosis to promote their survival and dissemination (16,30). While several E. coli serotypes (1, 4, 9, 15) and toxins (3, 19) have been shown to induce apoptosis of epithelial cells, the extent to which ETEC damages host cells is unclear. The prototypic ETEC isolate H10407 was cytotoxic to but failed to induce apoptosis in the macrophage cell line J774 (as measured by DNA fragmentation) (24). The extent to which LT induces apoptosis has also received considerable attention due to interest in the receptor-binding subunit (LT-B) as a mucosal adjuvant. LT-B induces apoptosis of CD8 ϩ but not CD4 ϩ T cells (37). Some studies indicate that binding of LT-B to GM1 may be sufficient for triggering apoptosis of CD8 ϩ T cells (33), while others suggest that modified LT-B constructs (e.g., H57S) still able to bind GM-1 may fail to trigger apoptosis (14). Yet other studies suggest that LT-mediated apoptosis requires the ADP-ribosylation activity of the LT-A subunit (41).Overall, the roles of ETEC and LT in mediating apoptosis have not been defined clearly and remain somewhat controversial. The goals of this study were therefore to quantify the ability of ETEC to damage porcine intestinal epithelial cells, to clarify the role of LT in these processes, and to me...

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“…Epithelial cell death is a well-known consequence of EPEC infection (32)(33)(34)(35)(36)(37). Furthermore, in human EPEC infection cases, pathological evidence of intestinal damage has been found (17,18,38).…”

Section: Discussionmentioning

confidence: 99%

EspC Promotes Epithelial Cell Detachment by Enteropathogenic Escherichia coli via Sequential Cleavages of a Cytoskeletal Protein and then Focal Adhesion Proteins

et al. 2014

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EspC is a non-locus of enterocyte effacement (LEE)-encoded autotransporter produced by enteropathogenic Escherichia coli (EPEC) that is secreted to the extracellular milieu by a type V secretion system and then translocated into epithelial cells by the type III secretion system. Here, we show that this efficient EspC delivery into the cell leads to a cytopathic effect characterized by cell rounding and cell detachment. Thus, EspC is the main protein involved in epithelial cell cytotoxicity detected during EPEC adhesion and pedestal formation assays. The cell detachment phenotype is triggered by cytoskeletal and focal adhesion disruption. EspC-producing EPEC is able to cleave fodrin, paxillin, and focal adhesion kinase (FAK), but these effects are not observed when cells are infected with an espC isogenic mutant. Recovery of these phenotypes by complementing the mutant with the espC gene but not with the espC gene mutated in the serine protease motif highlights the role of the protease activity of EspC in the cell detachment phenotype. In vitro assays using purified proteins showed that EspC, but not EspC with an S256I substitution [EspC S256I ], directly cleaves these cytoskeletal and focal adhesion proteins. Kinetics of protein degradation indicated that EspCproducing EPEC first cleaves fodrin (within the 11th and 9th repetitive units at the Q1219 and D938 residues, respectively), and this event sequentially triggers paxillin degradation, FAK dephosphorylation, and FAK degradation. Thus, cytoskeletal and focal adhesion protein cleavage leads to the cell rounding and cell detachment promoted by EspC-producing EPEC.

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Caspases-3, -8, and -9 are required for induction of epithelial cell apoptosis by enteropathogenic E. coli but are dispensable for increased paracellular permeability

Cited by 26 publications

References 32 publications

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

EnterotoxigenicEscherichia coliModulates Host Intestinal Cell Membrane Asymmetry and Metabolic Activity

EspC Promotes Epithelial Cell Detachment by Enteropathogenic Escherichia coli via Sequential Cleavages of a Cytoskeletal Protein and then Focal Adhesion Proteins

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