Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin
<i>Clostridioides difficile</i> infection is expected to become the most common healthcare-associated infection worldwide. <i>C. difficile</i>-induced pathogenicity is significantly attributed to its enterotoxin, TcdA, which primarily targets Rho-GTPases involved in regulatin...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/10/586 |
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| author | Maria Eleni Mavrogeni Mostafa Asadpoor Jo H. Judernatz Ingrid van Ark Marc M. S. M. Wösten Karin Strijbis Roland J. Pieters Gert Folkerts Saskia Braber |
| author_facet | Maria Eleni Mavrogeni Mostafa Asadpoor Jo H. Judernatz Ingrid van Ark Marc M. S. M. Wösten Karin Strijbis Roland J. Pieters Gert Folkerts Saskia Braber |
| author_sort | Maria Eleni Mavrogeni |
| collection | DOAJ |
| description | <i>Clostridioides difficile</i> infection is expected to become the most common healthcare-associated infection worldwide. <i>C. difficile</i>-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 <i>C. difficile</i> bacteria and TcdA toxin, respectively. Both NDOs significantly reduced <i>C. difficile</i> 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 <i>C. difficile</i> and its toxin, TcdA, while revealing their ability to promote TJ reassembly in Caco-2 cells. |
| first_indexed | 2024-03-10T20:50:32Z |
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| language | English |
| last_indexed | 2024-03-10T20:50:32Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-5b11f8c5a56e4b7d8753ec04e12aaf612023-11-19T18:22:20ZengMDPI AGToxins2072-66512023-09-01151058610.3390/toxins15100586Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and ToxinMaria Eleni Mavrogeni0Mostafa Asadpoor1Jo H. Judernatz2Ingrid van Ark3Marc M. S. M. Wösten4Karin Strijbis5Roland J. Pieters6Gert Folkerts7Saskia Braber8Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsStructural Biochemistry Group, Bijvoet Centre for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDivision of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The NetherlandsDivision of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The NetherlandsDivision of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands<i>Clostridioides difficile</i> infection is expected to become the most common healthcare-associated infection worldwide. <i>C. difficile</i>-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 <i>C. difficile</i> bacteria and TcdA toxin, respectively. Both NDOs significantly reduced <i>C. difficile</i> 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 <i>C. difficile</i> and its toxin, TcdA, while revealing their ability to promote TJ reassembly in Caco-2 cells.https://www.mdpi.com/2072-6651/15/10/586<i>C. difficile</i>TcdAAOSCOSintestinal epithelial barrierTJs |
| spellingShingle | Maria Eleni Mavrogeni Mostafa Asadpoor Jo H. Judernatz Ingrid van Ark Marc M. S. M. Wösten Karin Strijbis Roland J. Pieters Gert Folkerts Saskia Braber Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin Toxins <i>C. difficile</i> TcdA AOS COS intestinal epithelial barrier TJs |
| title | Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin |
| title_full | Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin |
| title_fullStr | Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin |
| title_full_unstemmed | Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin |
| title_short | Protective Effects of Alginate and Chitosan Oligosaccharides against <i>Clostridioides difficile</i> Bacteria and Toxin |
| title_sort | protective effects of alginate and chitosan oligosaccharides against i clostridioides difficile i bacteria and toxin |
| topic | <i>C. difficile</i> TcdA AOS COS intestinal epithelial barrier TJs |
| url | https://www.mdpi.com/2072-6651/15/10/586 |
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