ArticlePLoS pathogens2013
Enterohemorrhagic Escherichia coli hemolysin employs outer membrane vesicles to target mitochondria and cause endothelial and epithelial apoptosis.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 203 citations in OpenAlex.
- Substrate secretion by different EHEC secretion systems during their interaction with epithelial cells.Virulence · 2026Article
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- 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
- Outer membrane vesicles hijack TIM-1 for cellular uptake.PLoS pathogens · 2026Article
- 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
- Characterization ofIranian journal of microbiology · 2025Article
- Review on bacterial outer membrane vesicles: structure, vesicle formation, separation and biotechnological applications.Microbial cell factories · 2025Review
- EnterohemorrhagicFrontiers in cellular and infection microbiology · 2025Article
- Outer membrane vesicles in gram-negative bacteria and its correlation with pathogenesis.Frontiers in immunology · 2025Review
- Immune Responses Elicited by Outer Membrane Vesicles of Gram-Negative Bacteria: Important Players in Vaccine Development.Life (Basel, Switzerland) · 2024Review
- Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Antimicrobial Resistance and Pathotypes ofAnimals : an open access journal from MDPI · 2024Article
- An in-depth exploration of the multifaceted roles of EVs in the context of pathogenic single-cell microorganisms.Microbiology and molecular biology reviews : MMBR · 2024Review
- The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii.Nature communications · 2024Article
- Occurrence, serotypes and virulence characteristics of Shiga toxin-producing and Enteropathogenic Escherichia coli isolates from dairy cattle in South Africa.World journal of microbiology & biotechnology · 2024Article
- Microbiota-Derived Extracellular Vesicle as Emerging Actors in Host Interactions.International journal of molecular sciences · 2024Review
- Extracellular Membrane Vesicles ofMicroorganisms · 2024Article
- Multivariate Analysis of Individual Bacterial Outer Membrane Vesicles Using Fluorescence Microscopy.Chemical & biomedical imaging · 2024Article
- Extracellular Vesicles fromJournal of fungi (Basel, Switzerland) · 2024Article
- Pathogenomes of Shiga Toxin Positive and NegativeMicroorganisms · 2024Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enterohemorrhagic Escherichia coli (EHEC) strains cause diarrhea and hemolytic uremic syndrome resulting from toxin-mediated microvascular endothelial injury. EHEC hemolysin (EHEC-Hly), a member of the RTX (repeats-in-toxin) family, is an EHEC virulence factor of increasingly recognized importance. The toxin exists as free EHEC-Hly and as EHEC-Hly associated with outer membrane vesicles (OMVs) released by EHEC during growth. Whereas the free toxin is lytic towards human endothelium, the biological effects of the OMV-associated EHEC-Hly on microvascular endothelial and intestinal epithelial cells, which are the major targets during EHEC infection, are unknown. Using microscopic, biochemical, flow cytometry and functional analyses of human brain microvascular endothelial cells (HBMEC) and Caco-2 cells we demonstrate that OMV-associated EHEC-Hly does not lyse the target cells but triggers their apoptosis. The OMV-associated toxin is internalized by HBMEC and Caco-2 cells via dynamin-dependent endocytosis of OMVs and trafficked with OMVs into endo-lysosomal compartments. Upon endosome acidification and subsequent pH drop, EHEC-Hly is separated from OMVs, escapes from the lysosomes, most probably via its pore-forming activity, and targets mitochondria. This results in decrease of the mitochondrial transmembrane potential and translocation of cytochrome c to the cytosol, indicating EHEC-Hly-mediated permeabilization of the mitochondrial membranes. Subsequent activation of caspase-9 and caspase-3 leads to apoptotic cell death as evidenced by DNA fragmentation and chromatin condensation in the intoxicated cells. The ability of OMV-associated EHEC-Hly to trigger the mitochondrial apoptotic pathway in human microvascular endothelial and intestinal epithelial cells indicates a novel mechanism of EHEC-Hly involvement in the pathogenesis of EHEC diseases. The OMV-mediated intracellular delivery represents a newly recognized mechanism for a bacterial toxin to enter host cells in order to target mitochondria.
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