ArticlePLoS pathogens2017
Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 230 citations in OpenAlex.
- Induction of DNA-mediated immune responses by bacterial extracellular vesicles results in control of murine norovirus infection.Gut microbes · 2026Article
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- Bacterial Extracellular Vesicles at the Crossroads of Immune Regulation and Biofilm Dynamics: Biogenesis, Comparative Analysis, and Translational Challenges.Biomolecules · 2026Review
- Effect of gut bacterial extracellular vesicles on angiogenic potential and vascular integrity: positive and negative aspects.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Shiga toxin delivery in extracellular vesicles induces high mortality and severe kidney injury in a Gb3-dependent manner.PLoS pathogens · 2026Article
- Cellular effects of outer membrane vesicles isolated from pks-positive strains of bacteria.Research square · 2026Article
- Host Factor Induced Bacterial Extracellular Vesicles Promote Horizontal Gene Transfer in Vibrio cholerae.Journal of extracellular vesicles · 2026Article
- Outer membrane vesicles of carbapenem-resistantMicrobiology spectrum · 2026Article
- Engineered Escherichia coli as a microbial cell factory for intracellular protein delivery: strains, vectors, mechanisms, and therapeutic applications.Microbial cell factories · 2026Review
- Chlamydial membrane vesicles deliver the beta barrel outer membrane protein OmpA to mitochondria to inhibit apoptosis.PLoS pathogens · 2026Article
- Biophysical Features of Outer Membrane Vesicles (OMVs) from PathogenicAntibiotics (Basel, Switzerland) · 2026Article
- Bacterial outer membrane vesicles: a smart platform for biomedical applications.Cell communication and signaling : CCS · 2026Review
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- TM9SF4 acts as a receptor mediatingFrontiers in cellular and infection microbiology · 2026Article
- Small molecule inhibitor targets OmpV to treat pandemic Vibrio cholerae infection.Nature communications · 2025Article
- Investigating the activation of the immune response by outer membrane vesicles from Bacteroides fragilis using a human gastrointestinal cell system.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Predicting clinical outcome ofMicrobial genomics · 2025Article
- Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS-STING-IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization.Veterinary research · 2025Article
- Benzimidazole-Derived B2 as a Fluorescent Probe for Bacterial Outer Membrane Vesicle (OMV) Labeling: Integrating DFT, Molecular Dynamics, Flow Cytometry, and Confocal Microscopy.International journal of molecular sciences · 2025Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a), cytolethal distending toxin V (CdtV), EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs and differentially separate from vesicles during intracellular trafficking. Stx2a and CdtV-B, the DNase-like CdtV subunit, separate from OMVs in early endosomes. Stx2a is trafficked, in association with its receptor globotriaosylceramide within detergent-resistant membranes, to the Golgi complex and the endoplasmic reticulum from where the catalytic Stx2a A1 fragment is translocated to the cytosol. CdtV-B is, after its retrograde transport to the endoplasmic reticulum, translocated to the nucleus to reach DNA. CdtV-A and CdtV-C subunits remain OMV-associated and are sorted with OMVs to lysosomes. EHEC hemolysin separates from OMVs in lysosomes and targets mitochondria. The OMV-delivered CdtV-B causes cellular DNA damage, which activates DNA damage responses leading to G2 cell cycle arrest. The arrested cells ultimately die of apoptosis induced by Stx2a and CdtV via caspase-9 activation. By demonstrating that naturally secreted EHEC O157 OMVs carry and deliver into cells a cocktail of biologically active virulence factors, thereby causing cell death, and by performing first comprehensive analysis of intracellular trafficking of OMVs and OMV-delivered virulence factors, we provide new insights into the pathogenesis of EHEC O157 infections. Our data have implications for considering O157 OMVs as vaccine candidates.
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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.