Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.

Clostridioides difficile (C. difficile) infection is a major public health problem worldwide. The current treatment of C. difficile-associated diarrhea relies on the use of antibacterial agents. However, recurrences are frequent. The main virulence factors of C. difficile are two secreted cytotoxic...

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Autores principales:	Carmen Ranftler, Dietmar Nagl, Andreas Sparer, Andreas Röhrich, Michael Freissmuth, Ali El-Kasaby, Shahrooz Nasrollahi Shirazi, Florian Koban, Cornelius Tschegg, Stephane Nizet
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/47a6db82df864445b3eb786c493fdd27
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spelling	oai:doaj.org-article:47a6db82df864445b3eb786c493fdd272021-11-25T06:23:42ZBinding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.1932-620310.1371/journal.pone.0252211https://doaj.org/article/47a6db82df864445b3eb786c493fdd272021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252211https://doaj.org/toc/1932-6203Clostridioides difficile (C. difficile) infection is a major public health problem worldwide. The current treatment of C. difficile-associated diarrhea relies on the use of antibacterial agents. However, recurrences are frequent. The main virulence factors of C. difficile are two secreted cytotoxic proteins toxin A and toxin B. Alternative research exploring toxin binding by resins found a reduced rate of recurrence by administration of tolevamer. Hence, binding of exotoxins may be useful in preventing a relapse provided that the adsorbent is innocuous. Here, we examined the toxin binding capacity of G-PUR®, a purified version of natural clinoptilolite-tuff. Our observations showed that the purified clinoptilolite-tuff adsorbed clinically relevant amounts of C. difficile toxins A and B in vitro and neutralized their action in a Caco-2 intestinal model. This conclusion is based on four independent sets of findings: G-PUR® abrogated toxin-induced (i) RAC1 glucosylation, (ii) redistribution of occludin, (iii) rarefaction of the brush border as visualized by scanning electron microscopy and (iv) breakdown of the epithelial barrier recorded by transepithelial electrical resistance monitoring. Finally, we confirmed that the epithelial monolayer tolerated G-PUR® over a wide range of particle densities. Our findings justify the further exploration of purified clinoptilolite-tuff as a safe agent in the treatment and/or prevention of C. difficile-associated diarrhea.Carmen RanftlerDietmar NaglAndreas SparerAndreas RöhrichMichael FreissmuthAli El-KasabyShahrooz Nasrollahi ShiraziFlorian KobanCornelius TscheggStephane NizetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252211 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carmen Ranftler Dietmar Nagl Andreas Sparer Andreas Röhrich Michael Freissmuth Ali El-Kasaby Shahrooz Nasrollahi Shirazi Florian Koban Cornelius Tschegg Stephane Nizet Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.
description	Clostridioides difficile (C. difficile) infection is a major public health problem worldwide. The current treatment of C. difficile-associated diarrhea relies on the use of antibacterial agents. However, recurrences are frequent. The main virulence factors of C. difficile are two secreted cytotoxic proteins toxin A and toxin B. Alternative research exploring toxin binding by resins found a reduced rate of recurrence by administration of tolevamer. Hence, binding of exotoxins may be useful in preventing a relapse provided that the adsorbent is innocuous. Here, we examined the toxin binding capacity of G-PUR®, a purified version of natural clinoptilolite-tuff. Our observations showed that the purified clinoptilolite-tuff adsorbed clinically relevant amounts of C. difficile toxins A and B in vitro and neutralized their action in a Caco-2 intestinal model. This conclusion is based on four independent sets of findings: G-PUR® abrogated toxin-induced (i) RAC1 glucosylation, (ii) redistribution of occludin, (iii) rarefaction of the brush border as visualized by scanning electron microscopy and (iv) breakdown of the epithelial barrier recorded by transepithelial electrical resistance monitoring. Finally, we confirmed that the epithelial monolayer tolerated G-PUR® over a wide range of particle densities. Our findings justify the further exploration of purified clinoptilolite-tuff as a safe agent in the treatment and/or prevention of C. difficile-associated diarrhea.
format	article
author	Carmen Ranftler Dietmar Nagl Andreas Sparer Andreas Röhrich Michael Freissmuth Ali El-Kasaby Shahrooz Nasrollahi Shirazi Florian Koban Cornelius Tschegg Stephane Nizet
author_facet	Carmen Ranftler Dietmar Nagl Andreas Sparer Andreas Röhrich Michael Freissmuth Ali El-Kasaby Shahrooz Nasrollahi Shirazi Florian Koban Cornelius Tschegg Stephane Nizet
author_sort	Carmen Ranftler
title	Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.
title_short	Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.
title_full	Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.
title_fullStr	Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.
title_full_unstemmed	Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.
title_sort	binding and neutralization of c. difficile toxins a and b by purified clinoptilolite-tuff.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/47a6db82df864445b3eb786c493fdd27
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Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.

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