Protective Effects of Alginate and Chitosan Oligosaccharides against Clostridioides difficile Bacteria and Toxin

Clostridioides difficile infection is expected to become the most common healthcare-associated infection worldwide. C. difficile-induced pathogenicity is significantly attributed to its enterotoxin, TcdA, which primarily targets Rho-GTPases involved in regulating cytoskeletal and tight junction (TJ)...

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Bibliographic Details
Published in:Toxins 2023-09, Vol.15 (10), p.586
Main Authors: Mavrogeni, Maria Eleni, Asadpoor, Mostafa, Judernatz, Jo H., van Ark, Ingrid, Wösten, Marc M. S. M., Strijbis, Karin, Pieters, Roland J., Folkerts, Gert, Braber, Saskia
Format: Article
Language:English
Subjects:
Alginates
Alginic acid
Antibiotics
AOS
Assaying
Bacteria
C. difficile
Cell death
Chitosan
Clostridioides difficile
COS
Cytoskeleton
Cytotoxicity
Diarrhea
E coli
Guanine nucleotide-binding protein
Immunofluorescence
Inflammation
intestinal epithelial barrier
Microbiota
Monolayers
Oligosaccharides
Pathogenicity
Pathogens
Permeability
Prebiotics
Proteins
Staphylococcus infections
TcdA
TJs
Toxin A
Toxins
Zonula occludens-1 protein
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Summary:Clostridioides difficile infection is expected to become the most common healthcare-associated infection worldwide. C. difficile-induced pathogenicity is significantly attributed to its enterotoxin, TcdA, which primarily targets Rho-GTPases involved in regulating cytoskeletal and tight junction (TJ) dynamics, thus leading to cytoskeleton breakdown and ultimately increased intestinal permeability. This study investigated whether two non-digestible oligosaccharides (NDOs), alginate (AOS) and chitosan (COS) oligosaccharides, possess antipathogenic and barrier-protective properties against C. difficile bacteria and TcdA toxin, respectively. Both NDOs significantly reduced C. difficile growth, while cell cytotoxicity assays demonstrated that neither COS nor AOS significantly attenuated the TcdA-induced cell death 24 h post-exposure. The challenge of Caco-2 monolayers with increasing TcdA concentrations increased paracellular permeability, as measured by TEER and LY flux assays. In this experimental setup, COS completely abolished, and AOS mitigated, the deleterious effects of TcdA on the monolayer’s integrity. These events were not accompanied by alterations in ZO-1 and occludin protein levels; however, immunofluorescence microscopy revealed that both AOS and COS prevented the TcdA-induced occludin mislocalization. Finally, both NDOs accelerated TJ reassembly upon a calcium-switch assay. Overall, this study established the antipathogenic and barrier-protective capacity of AOS and COS against C. difficile and its toxin, TcdA, while revealing their ability to promote TJ reassembly in Caco-2 cells.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins15100586