ArticleProceedings of the National Academy of Sciences of the United States of America2010
NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 143 citations in OpenAlex.
- Serine phosphorylation of CesT by the type III secretion system effectors NleH1 and NleH2 regulates antagonization of CsrA in enteropathogenicInfection and immunity · 2026Article
- Modulation of host functions by bacterial serine/threonine protein kinase effector proteins.The Journal of biological chemistry · 2025Review
- Article
- Cell Death and Infection: Implications for Host and Microbe.Advances in experimental medicine and biology · 2025Review
- Article
- Molecular and Genomic Analysis of the Virulence Factors and Potential Transmission of Hybrid Enteropathogenic and EnterotoxigenicInternational journal of molecular sciences · 2023Article
- Bacterial effector kinases and strategies to identify their target host substrates.Frontiers in microbiology · 2023Review
- Review
- Targeting of microvillus protein Eps8 by the NleH effector kinases from enteropathogenicProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Reprogramming of Cell Death Pathways by Bacterial Effectors as a Widespread Virulence Strategy.Infection and immunity · 2022Review
- A nonredundant role for T cell-derived interleukin 22 in antibacterial defense of colonic crypts.Immunity · 2022Article
- Citrobacter rodentium(ϕStx2dact), a murine infection model for enterohemorrhagic Escherichia coli.Current opinion in microbiology · 2022Review
- Binding specificity of type three secretion system effector NleH2 to multi-cargo chaperone CesT and their phosphorylation.Protein science : a publication of the Protein Society · 2021Article
- The type III secretion system effector EspO of enterohaemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1.Cellular microbiology · 2021Article
- Identification of a Family ofmSphere · 2021Article
- Citrobacter rodentium Lysogenized with a Shiga Toxin-Producing Phage: A Murine Model for Shiga Toxin-Producing E. coli Infection.Methods in molecular biology (Clifton, N.J.) · 2021Article
- A unique bacterial tactic to circumvent the cell death crosstalk induced by blockade of caspase-8.The EMBO journal · 2020Article
- Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors.Cold Spring Harbor perspectives in biology · 2020Review
- Thinking outside of the cell: Secreted protein kinases in bacteria, parasites, and mammals.IUBMB life · 2019Review
- EPEC NleH1 is significantly more effective in reversing colitis and reducing mortality than NleH2 via differential effects on host signaling pathways.Laboratory investigation; a journal of technical methods and pathology · 2018Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The human pathogens enteropathogenic (EPEC) and enterohemorrhagic Escherichia coli and the related mouse pathogen Citrobacter rodentium subvert a variety of host cell signaling pathways via their plethora of type III secreted effectors, including triggering of an early apoptotic response. EPEC-infected cells do not develop late apoptotic symptoms, however. In this study we demonstrate that the NleH family effectors, homologs of the Shigella effector kinase OspG, blocks apoptosis. During EPEC infection, NleH effectors inhibit elevation of cytosolic Ca(2+) concentrations, nuclear condensation, caspase-3 activation, and membrane blebbing and promote cell survival. NleH1 alone is sufficient to prevent procaspase-3 cleavage induced by the proapoptotic compounds staurosporine, brefeldin A, and tunicamycin. Using C. rodentium, we found that NleH inhibits procaspase-3 cleavage at the bacterial attachment sites in vivo. A yeast two-hybrid screen identified the endoplasmic reticulum six-transmembrane protein Bax inhibitor-1 (BI-1) as an NleH-interacting partner. We mapped the NleH-binding site to the N-terminal 40 amino acids of BI-1. Knockdown of BI-1 resulted in the loss of NleH's antiapoptotic activity. These results indicate that NleH effectors are inhibitors of apoptosis that may act through BI-1 to carry out their cytoprotective 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.