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Toxins 2015, 7(11), 4610-4621; doi:10.3390/toxins7114610

Cell-to-Cell Propagation of the Bacterial Toxin CNF1 via Extracellular Vesicles: Potential Impact on the Therapeutic Use of the Toxin

1
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome 00161, Italy
2
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy
3
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Vernon L. Tesh
Received: 6 May 2015 / Revised: 21 October 2015 / Accepted: 2 November 2015 / Published: 5 November 2015
(This article belongs to the Section Bacterial Toxins)
View Full-Text   |   Download PDF [838 KB, uploaded 5 November 2015]   |  

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. View Full-Text
Keywords: extracellular vesicles; toxin transfer; intercellular communication; bacterial toxin; CNF1 extracellular vesicles; toxin transfer; intercellular communication; bacterial toxin; CNF1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Fabbri, A.; Cori, S.; Zanetti, C.; Guidotti, M.; Sargiacomo, M.; Loizzo, S.; Fiorentini, C. Cell-to-Cell Propagation of the Bacterial Toxin CNF1 via Extracellular Vesicles: Potential Impact on the Therapeutic Use of the Toxin. Toxins 2015, 7, 4610-4621.

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