Enteropathogenic
            <i>Escherichia coli</i>
            Type III Effectors EspG and EspG2 Disrupt the Microtubule Network of Intestinal Epithelial Cells

Shaw, Robert K.; Smollett, Katherine; Cleary, Jennifer; Garmendia, Junkal; Straatman-Iwanowska, Ania; Frankel, Gad; Knutton, Stuart

doi:10.1128/iai.73.7.4385-4390.2005

Cited by 64 publications

(68 citation statements)

References 26 publications

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“…Both EspG and EspG2 can independently activate RhoA in the host cell and increase paracellular permeability (43), besides being able to induce microtubule elimination (56). Map and EspF, two effector proteins that are not related at the sequence level, participate in EPEC-mediated disruption of epithelial barrier function, which can occur in the absence of Map or EspF but completely disappears in a map espF double mutant (13).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

et al. 2008

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Together with enterohemorrhagic Escherichia coli and enteropathogenic Escherichia coli, Citrobacter rodentium is a member of the attaching-and-effacing (A/E) family of bacterial pathogens. A/E pathogens use a type III secretion system (T3SS) to translocate an assortment of effector proteins, encoded both within and outside the locus of enterocyte effacement (LEE), into the colonized host cell, leading to the formation of A/E lesions and disease. Here we report the identification and characterization of a new non-LEE encoded effector, NleH, in C. rodentium. NleH is conserved among A/E pathogens and shares identity with OspG, a type III secreted effector protein in Shigella flexneri. Downstream of nleH, genes encoding homologues of the non-LEE-encoded effectors EspJ and NleG/NleI are found. NleH secretion and translocation into Caco-2 cells requires a functional T3SS and signals located at its amino-terminal domain. Transcription of nleH is not significantly reduced in mutants lacking the LEE-encoded regulators Ler and GrlA; however, NleH protein levels are highly reduced in these strains, as well as in escN and cesT mutants. Inactivation of Lon, but not of ClpP, protease restores NleH levels even in the absence of CesT. Our results indicate that the efficient engagement of NleH in active secretion is needed for its stability, thus establishing a posttranslational regulatory mechanism that coregulates NleH levels with the expression of LEE-encoded proteins. A C. rodentium nleH mutant shows a moderate defect during the colonization of C57BL/6 mice at early stages of infection.

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Section: Discussionmentioning

confidence: 99%

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

et al. 2008

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“…It has been shown that, like VirA, EspG disrupts microtubules in fibroblasts and nonpolarized epithelial cells (Shaw et al 2005). Interestingly, a study conducted by Elliott et al (2001) demonstrated that the EPEC espG gene can rescue invasion of a Shigella that contains a mutation inactivating virA.…”

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confidence: 99%

Novel fold of VirA, a type III secretion system effector protein from Shigella flexneri

Davis¹,

Wang

Tropea³

et al. 2008

Protein Science

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VirA, a secreted effector protein from Shigella sp., has been shown to be necessary for its virulence. It was also reported that VirA might be related to papain-like cysteine proteases and cleave a-tubulin, thus facilitating intracellular spreading. We have now determined the crystal structure of VirA at 3.0 Å resolution. The shape of the molecule resembles the letter ''V,'' with the residues in the N-terminal third of the 45-kDa molecule (some of which are disordered) forming one clearly identifiable domain, and the remainder of the molecule completing the V-like structure. The fold of VirA is unique and does not resemble that of any known protein, including papain, although its N-terminal domain is topologically similar to cysteine protease inhibitors such as stefin B. Analysis of the sequence conservation between VirA and its Escherichia coli homologs EspG and EspG2 did not result in identification of any putative protease-like active site, leaving open a possibility that the biological function of VirA in Shigella virulence may not involve direct proteolytic activity.

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“…Several recent studies have revealed that many effectors of A/E pathogens are encoded by genes carried on prophages and small pathogenicity islands which are nevertheless secreted and translocated into host cells by the LEE-encoded T3SS. These effectors include the Golgi-associated NleA/EspI, which is essential for full virulence of C. rodentium (19,29); EspJ, which may play a minor role in intestinal colonization (6); and EspG2, which, similarly to EspG, triggers the dissociation of microtubules beneath adherent bacteria (34). Other recent effectors show some strain and/or pathogen specificity, including the cycle inhibiting factor Cif, which induces host cell cycle arrest and reorganization of the actin cytoskeleton (4), and EspFU, or TccP (Tir-cytoskeleton coupling protein), which functions as an adapter protein of bacterial origin necessary for Tir-dependent recruitment and activation of N-WASP at the site of EHEC O157:H7 cell attachment (3,18).…”

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confidence: 99%

Essential Role of the Type III Secretion System Effector NleB in Colonization of Mice by Citrobacter rodentium

et al. 2006

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Attaching and effacing (A/E) pathogens are a significant cause of gastrointestinal illness in humans and animals. All A/E pathogens carry a large pathogenicity island, termed the locus for enterocyte effacement (LEE), which encodes a type III secretion system that translocates several effector proteins into host cells. To identify novel virulence determinants in A/E pathogens, we performed a signature-tagged mutagenesis screen in C57BL/6 mice by using the mouse A/E pathogen Citrobacter rodentium. Five hundred seventy-six derivatives of C. rodentium were tested in pools of 12 mutants. One attenuated mutant carried a transposon insertion in nleB, which encodes a putative effector of the LEE-encoded type III secretion system (T3SS). nleB is present in a genomic pathogenicity island that also encodes another putative effector, NleE, immediately downstream. Using translational fusions with ␤-lactamase (TEM-1), we showed that both NleB and NleE were translocated into host cells by the LEE-encoded T3SS of enteropathogenic Escherichia coli. In addition, deletion of the gene encoding NleB in C. rodentium resulted in reduced colonization of mice in single infections and reduced colonic hyperplasia. In contrast, the deletion of other non-LEE-encoded effector genes in C. rodentium, nleC, nleD, or nleE, had no effect on host colonization or disease. These results suggest that nleB encodes an important virulence determinant of A/E pathogens.

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Enteropathogenic Escherichia coli Type III Effectors EspG and EspG2 Disrupt the Microtubule Network of Intestinal Epithelial Cells

Cited by 64 publications

References 26 publications

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

Novel fold of VirA, a type III secretion system effector protein from Shigella flexneri

Essential Role of the Type III Secretion System Effector NleB in Colonization of Mice by Citrobacter rodentium

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