title: Cell-to-cell propagation of the bacterial toxin CNF1 via extracellular vesicles: potential impact on the therapeutic use of the toxin.
abstract: Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via EVs. We have herein demonstrated that eukaryotic EVs represent an additional route of cell-to-cell propagation for the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1). Our results prove that EVs from CNF1 pre-infected epithelial cells can induce cytoskeleton changes, Rac1 and NF-κB activation comparable to that triggered by CNF1. The observation that the toxin is detectable inside EVs derived from CNF1-intoxicated cells strongly supports the hypothesis that extracellular vesicles can offer to the toxin a novel route to travel from cell to cell. Since anthrax and tetanus toxins have also been reported to engage in the same process, we can hypothesize that EVs represent a common mechanism exploited by bacterial toxins to enhance their pathogenicity.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome 00161, Italy. alessia.fabbri@iss.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fabbri
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome 00161, Italy. sara_cori@hotmail.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Cori
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy. cristiana.zanetti@iss.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Zanetti
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy. marco.guidotti@iss.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Guidotti
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy. massimo.sargiacomo@iss.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sargiacomo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome 00161, Italy. stefano.loizzo@iss.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Loizzo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome 00161, Italy. carla.fiorentini@iss.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Fiorentini
mesh_terms: D001427:Bacterial Toxins / Q000494:pharmacology* / Q000627:therapeutic use*; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D000067128:Extracellular Vesicles / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D016328:NF-kappa B; C107953:RAC1 protein, human; C060296:cytotoxic necrotizing factor type 1; D020830:rac1 GTP-Binding Protein
keywords: CNF1; bacterial toxin; extracellular vesicles; intercellular communication; toxin transfer