Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

Grado, Myriam de; Abe, Akio; Gauthier, Annick; Steele‐Mortimer, Olivia; DeVinney, Rebekah; Finlay, B. Brett

doi:10.1046/j.1462-5822.1999.00001.x

Cited by 89 publications

(63 citation statements)

References 28 publications

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“…For example, following localization to the plasma membrane, SipA and SipC cooperate to cause actin polymerization and bundling at the cell surface, augmenting the ruffling necessary for the internalization of Salmonella cells (8,36,61). Likewise, Tir inserts into the plasma membrane so that an internal domain of the protein is exposed on the cell surface and accessible for binding by its bacterial ligand, intimin (9,27). In this regard, the localization of the phospholipase ExoU to the plasma membrane may have pathogenic relevance since this subcellular location is rich in phospholipids.…”

Section: Discussionmentioning

confidence: 99%

A C-Terminal Domain Targets the Pseudomonas aeruginosa Cytotoxin ExoU to the Plasma Membrane of Host Cells

Rabin¹,

Veesenmeyer²,

Bieging³

et al. 2006

Infect Immun

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ExoU, a phospholipase injected into host cells by the type III secretion system of Pseudomonas aeruginosa, leads to rapid cytolytic cell death. Although the importance of ExoU in infection is well established, the mechanism by which this toxin kills host cells is less clear. To gain insight into how ExoU causes cell death, we examined its subcellular localization following transfection or type III secretion/translocation into HeLa cells. Although rapid cell lysis precluded visualization of wild-type ExoU by fluorescence microscopy, catalytically inactive toxin was readily detected at the periphery of HeLa cells. Biochemical analysis confirmed that ExoU was targeted to the membrane fraction of transfected cells. Visualization of ExoU peptides fused with green fluorescent protein indicated that the domain responsible for this targeting was in the C terminus of ExoU, between residues 550 and 687. Localization to the plasma membrane occurred within 1 h of expression, which is consistent with the kinetics of cytotoxicity. Together, these results indicate that a domain between residues 550 and 687 of ExoU targets this toxin to the plasma membrane, a process that may be important in cytotoxicity.

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Section: Discussionmentioning

confidence: 99%

A C-Terminal Domain Targets the Pseudomonas aeruginosa Cytotoxin ExoU to the Plasma Membrane of Host Cells

Rabin¹,

Veesenmeyer²,

Bieging³

et al. 2006

Infect Immun

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“…A critical type III effector protein is Tir, which localizes in the host plasma membrane and acts as a receptor for the bacterial outer membrane protein intimin, promoting intimate adherence and filamentous actin assembly beneath bound bacteria (15)(16)(17)(18)(19). Both Tir and intimin are essential for colonization and virulence in several animal models of EHEC and Citrobacter infection (20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

A novel murine infection model for Shiga toxin–producing Escherichia coli

Mallick

McBee²,

Vanguri³

et al. 2012

J. Clin. Invest.

118

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Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates "attaching and effacing" (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease.

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“…These histologic lesions are defined by the intimate attachment of bacteria to the epithelial cell surface along with the localized loss (effacement) of microvilli and assembly of electrondense fibrillar structures underneath attached bacteria, forming a "pedestal-like" protrusion from the cell (33). Interactions between two LEE-encoded proteins, intimin and Tir (a T3SS effector that inserts into the host plasma membrane), are thought to mediate "intimate" adherence (8,18,23). Interactions between translocated Tir, EspF U (a T3SS effector protein encoded by the cryptic prophage CP-933U; also known as TccP), and host proteins are thought to promote actin polymerization in host cells, resulting in pedestal formation (3,15,31).…”

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confidence: 99%

Type 2 Secretion Promotes Enterohemorrhagic Escherichia coli Adherence and Intestinal Colonization

Davis

Ritchie

et al. 2008

Infect Immun

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Enterohemorrhagic Escherichia coli (EHEC) is a noninvasive food-borne pathogen that colonizes the distal ileum and colon. Proteins encoded in the EHEC locus of enterocyte effacement (LEE) pathogenicity island are known to contribute to this pathogen's adherence to epithelial cells and intestinal colonization. The role of non-LEE-encoded proteins in these processes is not as clear. We found that the Z2053 gene (designated adfO here), a gene located in a cryptic EHEC prophage, exhibits similarity to adherence and/or colonization factor genes found in several other enteric pathogens. An EHEC adfO mutant exhibited marked reductions in adherence to HeLa cells and in the secretion of several proteins into the supernatant. YodA, one of these secreted proteins, was found to be a substrate of the EHEC pO157-encoded type 2 secretion system (T2SS). Both the T2SS and YodA proved to be essential for EHEC adherence to cultured HeLa cell monolayers. Using an infant rabbit model of infection, we found that the adfO mutation did not affect colonization but that the colonization of an etpC (T2SS) mutant was reduced ϳ5-fold. A strain deficient in YodA had a more severe colonization defect; however, this strain also exhibited a growth defect in vitro. Overall, our findings indicate that the pO157-encoded T2SS contributes to EHEC adherence and intestinal colonization and thus show that EHEC pathogenicity depends on type 2 secretion as well as type 3 secretion.

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Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

Cited by 89 publications

References 28 publications

A C-Terminal Domain Targets the Pseudomonas aeruginosa Cytotoxin ExoU to the Plasma Membrane of Host Cells

A C-Terminal Domain Targets the Pseudomonas aeruginosa Cytotoxin ExoU to the Plasma Membrane of Host Cells

A novel murine infection model for Shiga toxin–producing Escherichia coli

Type 2 Secretion Promotes Enterohemorrhagic Escherichia coli Adherence and Intestinal Colonization

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