Retraction of enteropathogenic E. coli type IV pili promotes efficient host cell colonization, effector translocation and tight junction disruption

Aroeti, Benjamin; Friedman, Gil; Zlotkin-Rivkin, Efrat; Donnenberg, Michael S.

doi:10.4161/gmic.19814

Cited by 23 publications

(24 citation statements)

References 49 publications

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“…This altered TJ function occurs through direct effects of EPEC infection on the IEC cytoskeleton (10,65) and via the indirect action of EPEC-induced proinflammatory cytokines (17,66). In light of our data indicating that induction of endogenous IFN-␤ or treatment with exogenous IFN resulted in protection from EPEC-induced barrier disruption (Fig.…”

Section: Ifn-␤ Protects From Epec-induced Barrier Disruption and Regumentioning

confidence: 89%

“…In the first step of infection, adhesive type IV bundleforming pili allow EPEC to bind IECs and form aggregates. Intimate attachment of EPEC to the IEC membrane initiates the formation of actin-rich pedestals and disrupts TJ function (10). Specifically, ZO-1 is dislocated, causing endocytosis and dephosphorylation of occludin (11) and contraction of the perijunctional actin-myosin ring (12).…”

mentioning

confidence: 99%

“…Specifically, ZO-1 is dislocated, causing endocytosis and dephosphorylation of occludin (11) and contraction of the perijunctional actin-myosin ring (12). Retraction of the pili facilitates injection of type III secretion system (T3SS) effector proteins directly into the cytosol (10). T3SS effectors mediate sustained loss of barrier function by targeting TJs and subvert the host immune response via multiple mechanisms (13).…”

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confidence: 99%

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Enteropathogenic Escherichia coli Inhibits Type I Interferon- and RNase L-Mediated Host Defense To Disrupt Intestinal Epithelial Cell Barrier Function

et al. 2014

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EnteropathogenicEscherichia coli(EPEC) primarily infects children in developing countries and causes diarrhea that can be deadly. EPEC pathogenesis occurs through type III secretion system (T3SS)-mediated injection of effectors into intestinal epithelial cells (IECs); these effectors alter actin dynamics, modulate the immune response, and disrupt tight junction (TJ) integrity. The resulting compromised barrier function and increased gastrointestinal (GI) permeability may be responsible for the clinical symptoms of infection. Type I interferon (IFN) mediates anti-inflammatory activities and serves essential functions in intestinal immunity and homeostasis; however, its role in the immune response to enteric pathogens, such as EPEC, and its impact on IEC barrier function have not been examined. Here, we report that IFN-β is induced following EPEC infection and regulates IEC TJ proteins to maintain barrier function. The EPEC T3SS effector NleD counteracts this protective activity by inhibiting IFN-β induction and enhancing tumor necrosis factor alpha to promote barrier disruption. The endoribonuclease RNase L is a key mediator of IFN induction and action that promotes TJ protein expression and IEC barrier integrity. EPEC infection inhibits RNase L in a T3SS-dependent manner, providing a mechanism by which EPEC evades IFN-induced antibacterial activities. This work identifies novel roles for IFN-β and RNase L in IEC barrier functions that are targeted by EPEC effectors to escape host defense mechanisms and promote virulence. The IFN-RNase L axis thus represents a potential therapeutic target for enteric infections and GI diseases involving compromised barrier function.

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Section: Ifn-␤ Protects From Epec-induced Barrier Disruption and Regumentioning

confidence: 89%

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confidence: 99%

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confidence: 99%

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Enteropathogenic Escherichia coli Inhibits Type I Interferon- and RNase L-Mediated Host Defense To Disrupt Intestinal Epithelial Cell Barrier Function

et al. 2014

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“…The altered microbiota might have contributed to the prolonged effects in vivo. The ability of pathogenic strains of E.coli to disrupt TJ structures and epithelial barriers is well known (27). E. coli, a major constituent ofthe oral microbiota in the animals treated with DSS, P. gingivalis, or both, might have had a similar effect on TJ structure.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas Gingivalisand Dextran Sulfate Sodium Induce Periodontitis Through the Disruption of Physical Barriers in Mice

Choi

Kim

et al. 2013

Eur J Inflamm

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Periodontitis is a chronic inflammatory disease caused by the interaction of plaque-associated bacteria with host cells. Gingival epithelial barriers provide the first line of defense against plaque-associated bacteria, the primary cause of periodontitis. To investigate the role of physical barriers in the pathogenesis of periodontitis, dextran sulfate sodium (DSS), a tight junction (TJ)-disrupting chemical, was applied onto the gingival mucosa of mice in the absence or presence of Porphyromonas gingivalis, and alveolar bone loss was measured. The levels of the TJ proteins ZO-1 and JAM-1, the number of T cells, and the presence of bacteria within gingival tissue were examined by immunohistochemistry and in situ hybridization, respectively. In addition, oral bacterial communities were analyzed by pyrosequencing. Here, we show that both DSS and P. gingivalis induced alveolar bone loss accompanied by the reduced ZO-1 expression in the junctional epithelia. This reduction in ZO-1 expression was associated with increased levels of bacteria and T cells within the gingival tissues. Furthermore, bacterial invasion was strongly correlated with T-cell infiltration, which was associated with alveolar bone loss. Interestingly, both DSS and P. gingivalis shifted oral flora from Proteus-dominant community to Escherichia-dominant ones. Collectively, these findings suggest that a barrier-disrupting periodontal pathogen or chemical can induce periodontitis by facilitating bacterial invasion into tissues, leading to a subsequent inflammatory response. The association between compromised physical barriers and periodontitis was further supported by the reduction of ZO-1 expression in the periodontal lesions of patients with chronic periodontitis. Therefore, physical barriers may be a promising future target for the prevention and treatment of periodontitis.

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“…In fact, some of the differences in the two classes of assembly systems may be related in part to the evolution of T4aP into an efficient motility apparatus. There are a few reports providing evidence that the T4b bundle-forming pili of EPEC (which has a PilT homolog) can retract (21,192,428), but they are not involved in twitching motility. Other modes of T4aP-dependent movement, including "walking" and "slingshot" motilities, have recently been reported for P. aeruginosa; all modes depend on pilus retraction (108,153).…”

Section: Motilitymentioning

confidence: 99%

Type IV Pilin Proteins: Versatile Molecular Modules

Giltner

Nguyen

Burrows

2012

Microbiol Mol Biol Rev

410

519

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SUMMARYType IV pili (T4P) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. The major subunit of T4P is the type IV pilin, and structurally related proteins are found as components of the type II secretion (T2S) system, where they are called pseudopilins; of DNA uptake/competence systems in both Gram-negative and Gram-positive species; and of flagella, pili, and sugar-binding systems in the archaea. This broad distribution of a single protein family implies both a common evolutionary origin and a highly adaptable functional plan. The type IV pilin is a remarkably versatile architectural module that has been adopted widely for a variety of functions, including motility, attachment to chemically diverse surfaces, electrical conductance, acquisition of DNA, and secretion of a broad range of structurally distinct protein substrates. In this review, we consider recent advances in this research area, from structural revelations to insights into diversity, posttranslational modifications, regulation, and function.

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Retraction of enteropathogenic E. coli type IV pili promotes efficient host cell colonization, effector translocation and tight junction disruption

Cited by 23 publications

References 49 publications

Enteropathogenic Escherichia coli Inhibits Type I Interferon- and RNase L-Mediated Host Defense To Disrupt Intestinal Epithelial Cell Barrier Function

Enteropathogenic Escherichia coli Inhibits Type I Interferon- and RNase L-Mediated Host Defense To Disrupt Intestinal Epithelial Cell Barrier Function

Porphyromonas Gingivalisand Dextran Sulfate Sodium Induce Periodontitis Through the Disruption of Physical Barriers in Mice

Type IV Pilin Proteins: Versatile Molecular Modules

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