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Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers

One of the characteristic manifestations of Shiga-toxin-producing Escherichia coli (E. coli) infection in humans, including EHEC and Enteroaggregative E. coli O104:H4, is watery diarrhea. However, neither Shiga toxin nor numerous components of the type-3 secretion system have been found to independe...

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Autores principales: Tse, C. Ming, In, Julie G., Yin, Jianyi, Donowitz, Mark, Doucet, Michele, Foulke-Abel, Jennifer, Ruiz-Perez, Fernando, Nataro, James P., Zachos, Nicholas C., Kaper, James B., Kovbasnjuk, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162544/
https://www.ncbi.nlm.nih.gov/pubmed/30200426
http://dx.doi.org/10.3390/toxins10090351
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author Tse, C. Ming
In, Julie G.
Yin, Jianyi
Donowitz, Mark
Doucet, Michele
Foulke-Abel, Jennifer
Ruiz-Perez, Fernando
Nataro, James P.
Zachos, Nicholas C.
Kaper, James B.
Kovbasnjuk, Olga
author_facet Tse, C. Ming
In, Julie G.
Yin, Jianyi
Donowitz, Mark
Doucet, Michele
Foulke-Abel, Jennifer
Ruiz-Perez, Fernando
Nataro, James P.
Zachos, Nicholas C.
Kaper, James B.
Kovbasnjuk, Olga
author_sort Tse, C. Ming
collection PubMed
description One of the characteristic manifestations of Shiga-toxin-producing Escherichia coli (E. coli) infection in humans, including EHEC and Enteroaggregative E. coli O104:H4, is watery diarrhea. However, neither Shiga toxin nor numerous components of the type-3 secretion system have been found to independently elicit fluid secretion. We used the adult stem-cell-derived human colonoid monolayers (HCM) to test whether EHEC-secreted extracellular serine protease P (EspP), a member of the serine protease family broadly expressed by diarrheagenic E. coli can act as an enterotoxin. We applied the Ussing chamber/voltage clamp technique to determine whether EspP stimulates electrogenic ion transport indicated by a change in short-circuit current (Isc). EspP stimulates Isc in HCM. The EspP-stimulated Isc does not require protease activity, is not cystic fibrosis transmembrane conductance regulator (CFTR)-mediated, but is partially Ca(2+)-dependent. EspP neutralization with a specific antibody reduces its potency in stimulating Isc. Serine Protease A, secreted by Enteroaggregative E. coli, also stimulates Isc in HCM, but this current is CFTR-dependent. In conclusion, EspP stimulates colonic CFTR-independent active ion transport and may be involved in the pathophysiology of EHEC diarrhea. Serine protease toxins from E. coli pathogens appear to serve as enterotoxins, potentially significantly contributing to watery diarrhea.
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spelling pubmed-61625442018-10-03 Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers Tse, C. Ming In, Julie G. Yin, Jianyi Donowitz, Mark Doucet, Michele Foulke-Abel, Jennifer Ruiz-Perez, Fernando Nataro, James P. Zachos, Nicholas C. Kaper, James B. Kovbasnjuk, Olga Toxins (Basel) Article One of the characteristic manifestations of Shiga-toxin-producing Escherichia coli (E. coli) infection in humans, including EHEC and Enteroaggregative E. coli O104:H4, is watery diarrhea. However, neither Shiga toxin nor numerous components of the type-3 secretion system have been found to independently elicit fluid secretion. We used the adult stem-cell-derived human colonoid monolayers (HCM) to test whether EHEC-secreted extracellular serine protease P (EspP), a member of the serine protease family broadly expressed by diarrheagenic E. coli can act as an enterotoxin. We applied the Ussing chamber/voltage clamp technique to determine whether EspP stimulates electrogenic ion transport indicated by a change in short-circuit current (Isc). EspP stimulates Isc in HCM. The EspP-stimulated Isc does not require protease activity, is not cystic fibrosis transmembrane conductance regulator (CFTR)-mediated, but is partially Ca(2+)-dependent. EspP neutralization with a specific antibody reduces its potency in stimulating Isc. Serine Protease A, secreted by Enteroaggregative E. coli, also stimulates Isc in HCM, but this current is CFTR-dependent. In conclusion, EspP stimulates colonic CFTR-independent active ion transport and may be involved in the pathophysiology of EHEC diarrhea. Serine protease toxins from E. coli pathogens appear to serve as enterotoxins, potentially significantly contributing to watery diarrhea. MDPI 2018-09-01 /pmc/articles/PMC6162544/ /pubmed/30200426 http://dx.doi.org/10.3390/toxins10090351 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tse, C. Ming
In, Julie G.
Yin, Jianyi
Donowitz, Mark
Doucet, Michele
Foulke-Abel, Jennifer
Ruiz-Perez, Fernando
Nataro, James P.
Zachos, Nicholas C.
Kaper, James B.
Kovbasnjuk, Olga
Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers
title Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers
title_full Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers
title_fullStr Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers
title_full_unstemmed Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers
title_short Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers
title_sort enterohemorrhagic e. coli (ehec)—secreted serine protease espp stimulates electrogenic ion transport in human colonoid monolayers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162544/
https://www.ncbi.nlm.nih.gov/pubmed/30200426
http://dx.doi.org/10.3390/toxins10090351
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