The enteropathogenic E. coli effector EspH promotes actin pedestal formation and elongation via WASP-interacting protein (WIP)

Wong, Alexander R. C.; Raymond, Benoît; Collins, James W.; Crepin, Valérie F.; Frankel, Gad

doi:10.1111/j.1462-5822.2012.01778.x

Cited by 34 publications

(26 citation statements)

References 58 publications

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“…Like Map, EspF localizes to mitochondria (114) and has been shown to disrupt tight junctions (115), while EspG alters host cytoskeletal components through its interaction with tubulin (116). EspZ promotes host cell survival (117), whereas EspH affects filopodium formation, participates in actin signaling during pedestal formation (118), and acts as a RhoGEF inhibitor (119). Both EspH and EspB are capable of inhibiting phagocytosis of EPEC by macrophages (120,121).…”

Section: Pathogenesismentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli .

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Section: Pathogenesismentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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“…51,52 EspH has been shown to promote actin polymerization and this function is inhibited by a dominant negative isoform of WASP-interacting protein (WIP). 53 WIP binds to N-WASP WH1 domain to inhibit the EspH activity in actin dynamics. On the other hand, EspH recruits N-WASP and Arp2/3 to the site of bacterial attachment.…”

Section: Manipulation Of Host Cellular and Subcellular Targets By E mentioning

confidence: 99%

Effector triggered manipulation of host immune response elicited by different pathotypes ofEscherichia coli

Jayamani

Mylonakis

2014

Virulence

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Effectors are virulence factors that are secreted by bacteria during an infection in order to subvert cellular processes or induce the surveillance system of the host. Pathogenic microorganisms encode effectors, toxins and components of secretion systems that inject the effectors to the host. Escherichia coli is part of the innocuous commensal microbial flora of the gastrointestinal tract. However, pathogenic E. coli can cause diarrheal and extraintestinal diseases. Pathogenic E. coli uses secretion systems to inject an array of effector proteins directly into the host cells. Herein, we discuss the effectors secreted by different pathotypes of E. coli and provide an overview of strategies employed by effectors to target the host cellular and subcellular processes as well as their role in triggering host immune response.

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“…Fortunately, the EspC-FAK interaction in vitro allowed us to detect amino-and carboxy-terminal degradation subproducts by using antibodies against either of these ends, suggesting that further FAK degradation in the cells could be occurring by means of other host proteases. It is worth mentioning that EspC is the most prominent protein secreted by EPEC before the T3SS translocator proteins (25), and unlike other cytotoxic LEE effectors, such as EspF, Map, and EspH (32,43,44), EspC is not subject to the T3SS timing for its secretion (45). On the other hand, the paxillin 35-kDa subproduct detected during EPEC infection, which appears to be derived from ␤-paxillin, was not detected during the EspC-paxillin interaction in vitro, where the main degraded isoform was ␣-paxillin.…”

Section: Figmentioning

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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The enteropathogenic E. coli effector EspH promotes actin pedestal formation and elongation via WASP-interacting protein (WIP)

Cited by 34 publications

References 58 publications

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Effector triggered manipulation of host immune response elicited by different pathotypes ofEscherichia coli

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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