ArticlePLoS pathogens2011
The enteropathogenic E. coli (EPEC) Tir effector inhibits NF-κB activity by targeting TNFα receptor-associated factors.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 61 citations in OpenAlex.
- Intrinsic Disorder as a New Frontier in Antimicrobial Resistance and Bacterial Fitness.MicrobiologyOpen · 2026Review
- EnteropathogeniceLife · 2026Article
- Intestinal Goblet Cell-Expressed Reg4 Ameliorates Intestinal Inflammation Potentially by Restraining Pathogenic Escherichia coli Infection.Probiotics and antimicrobial proteins · 2025Article
- Catalytic DxD motif caged in Asx-turn and Met-aromatic interaction attenuates the pathogenic glycosylation of SseK2/NleB2 effectors.Scientific reports · 2022Article
- The Galleria mellonella-Enteropathogenic Escherichia coli Model System: Characterization of Pathogen Virulence and Insect Immune Responses.Journal of insect science (Online) · 2021Article
- Article
- Clustering of Tir during enteropathogenic E. coli infection triggers calcium influx-dependent pyroptosis in intestinal epithelial cells.PLoS biology · 2020Article
- Type III Secretion Effectors with Arginine N-Glycosyltransferase Activity.Microorganisms · 2020Review
- Bacteria-Catalyzed Arginine Glycosylation in Pathogens and Host.Frontiers in cellular and infection microbiology · 2020Review
- Worm-Based Alternate Assessment of Probiotic Intervention against Gut Barrier Infection.Nutrients · 2019Article
- SseK1 and SseK3 Type III Secretion System Effectors Inhibit NF-κB Signaling and Necroptotic Cell Death in Salmonella-Infected Macrophages.Infection and immunity · 2017Article
- Modulation of host signaling in the inflammatory response by enteropathogenic Escherichia coli virulence proteins.Cellular & molecular immunology · 2017Review
- Article
- Diarrheagenic Escherichia coli.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2016Review
- Identification of a Distinct Substrate-binding Domain in the Bacterial Cysteine Methyltransferase Effectors NleE and OspZ.The Journal of biological chemistry · 2016Article
- Interleukin-8, CXCL1, and MicroRNA miR-146a Responses to Probiotic Escherichia coli Nissle 1917 and Enteropathogenic E. coli in Human Intestinal Epithelial T84 and Monocytic THP-1 Cells after Apical or Basolateral Infection.Infection and immunity · 2016Article
- Escherichia coli Type III Secretion System 2 ATPase EivC Is Involved in the Motility and Virulence of Avian Pathogenic Escherichia coli.Frontiers in microbiology · 2016Article
- Modulation of the Inflammasome Signaling Pathway by Enteropathogenic and Enterohemorrhagic Escherichia coli.Frontiers in cellular and infection microbiology · 2016Review
- Novel Host Proteins and Signaling Pathways in Enteropathogenic E. coli Pathogenesis Identified by Global Phosphoproteome Analysis.Molecular & cellular proteomics : MCP · 2015Article
- Contribution of Crk adaptor proteins to host cell and bacteria interactions.BioMed research international · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Enteropathogenic Escherichia coli (EPEC) disease depends on the transfer of effector proteins into epithelia lining the human small intestine. EPEC E2348/69 has at least 20 effector genes of which six are located with the effector-delivery system genes on the Locus of Enterocyte Effacement (LEE) Pathogenicity Island. Our previous work implied that non-LEE-encoded (Nle) effectors possess functions that inhibit epithelial anti-microbial and inflammation-inducing responses by blocking NF-κB transcription factor activity. Indeed, screens by us and others have identified novel inhibitory mechanisms for NleC and NleH, with key co-operative functions for NleB1 and NleE1. Here, we demonstrate that the LEE-encoded Translocated-intimin receptor (Tir) effector has a potent and specific ability to inhibit NF-κB activation. Indeed, biochemical, imaging and immunoprecipitation studies reveal a novel inhibitory mechanism whereby Tir interaction with cytoplasm-located TNFα receptor-associated factor (TRAF) adaptor proteins induces their proteasomal-independent degradation. Infection studies support this Tir-TRAF relationship but reveal that Tir, like NleC and NleH, has a non-essential contribution in EPEC's NF-κB inhibitory capacity linked to Tir's activity being suppressed by undefined EPEC factors. Infections in a disease-relevant intestinal model confirm key NF-κB inhibitory roles for the NleB1/NleE1 effectors, with other studies providing insights on host targets. The work not only reveals a second Intimin-independent property for Tir and a novel EPEC effector-mediated NF-κB inhibitory mechanism but also lends itself to speculations on the evolution of EPEC's capacity to inhibit NF-κB function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.