Title (en)
Bacillus cereus extracellular vesicles act as shuttles for biologically active multicomponent enterotoxins
Language
English
Description (en)
Extracellular vesicles (EVs) from Gram-positive bacteria have gained considerable importance as a novel transport system of virulence factors in host-pathogen interactions. Bacillus cereus is a Gram-positive human pathogen, causing gastrointestinal toxemia as well as local and systemic infections. The pathogenicity of enteropathogenic B. cereus has been linked to a collection of virulence factors and exotoxins. Nevertheless, the exact mechanism of virulence factor secretion and delivery to target cells is poorly understood.Here, we investigate the production and characterization of enterotoxin-associated EVs from the enteropathogenic B. cereus strain NVH0075-95 by using a proteomics approach and studied their interaction with human host cells in vitro. For the first time, comprehensive analyses of B. cereus EV proteins revealed virulence-associated factors, such as sphingomyelinase, phospholipase C, and the three-component enterotoxin Nhe. The detection of Nhe subunits was confirmed by immunoblotting, showing that the low abundant subunit NheC was exclusively detected in EVs as compared to vesicle-free supernatant. Cholesterol-dependent fusion and predominantly dynamin-mediated endocytosis of B. cereus EVs with the plasma membrane of intestinal epithelial Caco2 cells represent entry routes for delivery of Nhe components to host cells, which was assessed by confocal microscopy and finally led to delayed cytotoxicity. Furthermore, we could show that B. cereus EVs elicit an inflammatory response in human monocytes and contribute to erythrocyte lysis via a cooperative interaction of enterotoxin Nhe and sphingomyelinase.Our results provide insights into the interaction of EVs from B. cereus with human host cells and add a new layer of complexity to our understanding of multicomponent enterotoxin assembly, offering new opportunities to decipher molecular processes involved in disease development.
Keywords (en)
Membrane-Derived Vesicles; Gram-Positive Bacteria; Phospholipase-C; Hemolysin Bl; Virulence Factors; Nhe Enterotoxin; Sphingomyelinase; Cytotoxicity; Biogenesis; Antibodies
DOI
10.1186/s12964-023-01132-1
Author of the digital object
Tanja Buchacher (University of Veterinary Medicine Vienna)
Monika Ehling-Schulz (University of Veterinary Medicine Vienna)
Giorgia Del Favero (University of Vienna)
Astrid Digruber (University of Veterinary Medicine Vienna)
Markus Kanzler (University of Veterinary Medicine Vienna)
Format
application/pdf
Size
1.2 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Cell Communication and Signaling
Pages or Volume
17
Volume
21
Number
1
Publisher
BMC
Publication Date
2023
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Persistent identifier
DOI
https://phaidra.vetmeduni.ac.at/o:2307
https://doi.org/10.1186/s12964-023-01132-1 - Content
- DetailsObject typePDFDocumentFormatapplication/pdfCreated14.11.2023 09:29:05
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