Cortactin Recruitment by Enterohemorrhagic
            <i>Escherichia coli</i>
            O157:H7 during Infection In Vitro and Ex Vivo

Mousnier, Aurélie; Whale, Andrew; Schüller, Stephanie; Leong, John M.; Phillips, Alan D.; Frankel, Gad

doi:10.1128/iai.00140-08

Cited by 14 publications

(15 citation statements)

References 26 publications

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“…Cells were seeded onto glass coverslips in 24‐well plates at a density of 5 × 10 4 cells per well, 48 h before infection. EHEC (Mousnier et al. , 2008) or C. rodentium (Girard et al.…”

Section: Methodsmentioning

confidence: 99%

Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo

Crepin

Girard

Schüller

et al. 2010

Molecular Microbiology

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Attaching and effacing (A/E) lesions and actin polymerization, the hallmark of enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC) and Citrobacter rodentium (CR) infections, are dependent on the effector Tir. Phosphorylation of TirEPEC/CR Y474/1 leads to recruitment of Nck and neural Wiskott–Aldrich syndrome protein (N-WASP) and strong actin polymerization in cultured cells. TirEPEC/CR also contains an Asn-Pro-Tyr (NPY454/1) motif, which triggers weak actin polymerization. In EHEC the NPY458 actin polymerization pathway is amplified by TccP/EspFU, which is recruited to Tir via IRSp53 and/or insulin receptor tyrosine kinase substrate (IRTKS). Here we used C. rodentium to investigate the different Tir signalling pathways in vivo. Following infection with wild-type C. rodentium IRTKS, but not IRSp53, was recruited to the bacterial attachment sites. Similar results were seen after infection of human ileal explants with EHEC. Mutating Y471 or Y451 in TirCR abolished recruitment of Nck and IRTKS respectively, but did not affect recruitment of N-WASP or A/E lesion formation. This suggests that despite their crucial role in actin polymerization in cultured cells the Tir:Nck and Tir:IRTKS pathways are not essential for N-WASP recruitment or A/E lesion formation in vivo. Importantly, wild-type C. rodentium out-competed the tir tyrosine mutants during mixed infections. These results uncouple the Tir:Nck and Tir:IRTKS pathways from A/E lesion formation in vivo but assign them an important in vivo role.

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“…Cells were seeded onto glass coverslips in 24‐well plates at a density of 5 × 10 4 cells per well, 48 h before infection. EHEC (Mousnier et al. , 2008) or C. rodentium (Girard et al.…”

Section: Methodsmentioning

confidence: 99%

Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo

Crepin

Girard

Schüller

et al. 2010

Molecular Microbiology

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“…Phillips and coworkers have established an IVOC from pediatric biopsy specimens of duodenum mounted in a modified MicroSnapwell system specifically adapted for use with 2-to 3-mmdiameter biopsy samples. This IVOC system has been used mainly to study the mechanisms of virulence of ETEC (839), EPEC (840)(841)(842)(843)(844)(845)(846)(847)(848)(849)(850)(851), EHEC (852)(853)(854)(855)(856)(857), EAEC (507,858), and Salmonella (392) and the action of Stx toxins (641). Other IVOCs have been used for studies on C. jejuni (859), EPEC (692,860,861), EAEC (645,(862)(863)(864), and Shigella (865) pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

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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“…It has been previously suggested that EHEC infection may trigger multiple pathways of actin assembly in host cells [35,36]. Data presented here indicate that actin remodeling necessary for MPC differs from that involved in EHEC intimate attachment to the enterocytes, which is a T3SS-dependent process.…”

Section: Resultsmentioning

confidence: 61%

“…Data presented here indicate that actin remodeling necessary for MPC differs from that involved in EHEC intimate attachment to the enterocytes, which is a T3SS-dependent process. It has been shown that EHEC controls attachment to the host cells through a tightly regulated balance between tyrosine phosphorylation and dephosphorylation of cortactin, the F-actin binding protein which is involved in pedestal formation [36–38]. This occurs through direct binding between phosphorylated cortactin (p-cortactin) and the T3SS effectors Tir and EspFu.…”

Section: Resultsmentioning

confidence: 99%

Serine Protease EspP from Enterohemorrhagic Escherichia Coli Is Sufficient to Induce Shiga Toxin Macropinocytosis in Intestinal Epithelium

Lukyanenko

Foulke‐Abel

et al. 2013

PLoS ONE

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Life-threatening intestinal and systemic effects of the Shiga toxins produced by enterohemorrhagic Escherichia coli (EHEC) require toxin uptake and transcytosis across intestinal epithelial cells. We have recently demonstrated that EHEC infection of intestinal epithelial cells stimulates toxin macropinocytosis, an actin-dependent endocytic pathway. Host actin rearrangement necessary for EHEC attachment to enterocytes is mediated by the type 3 secretion system which functions as a molecular syringe to translocate bacterial effector proteins directly into host cells. Actin-dependent EHEC attachment also requires the outer membrane protein intimin, a major EHEC adhesin. Here, we investigate the role of type 3 secretion in actin turnover occurring during toxin macropinocytosis. Toxin macropinocytosis is independent of EHEC type 3 secretion and intimin attachment. EHEC soluble factors are sufficient to stimulate macropinocytosis and deliver toxin into enterocytes in vitro and in vivo; intact bacteria are not required. Intimin-negative enteroaggregative Escherichia coli (EAEC) O104:H4 robustly stimulate Shiga toxin macropinocytosis into intestinal epithelial cells. The apical macropinosomes formed in intestinal epithelial cells move through the cells and release their cargo at these cells’ basolateral sides. Further analysis of EHEC secreted proteins shows that a serine protease EspP alone is able to stimulate host actin remodeling and toxin macropinocytosis. The observation that soluble factors, possibly serine proteases including EspP, from each of two genetically distinct toxin-producing strains, can stimulate Shiga toxin macropinocytosis and transcellular transcytosis alters current ideas concerning mechanisms whereby Shiga toxin interacts with human enterocytes. Mechanisms important for this macropinocytic pathway could suggest new potential therapeutic targets for Shiga toxin-induced disease.

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Cortactin Recruitment by Enterohemorrhagic Escherichia coli O157:H7 during Infection In Vitro and Ex Vivo

Cited by 14 publications

References 26 publications

Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo

Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo

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

Serine Protease EspP from Enterohemorrhagic Escherichia Coli Is Sufficient to Induce Shiga Toxin Macropinocytosis in Intestinal Epithelium

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