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dc.contributor.authorFoulke-Abel, J.
dc.contributor.authorYu, H.
dc.contributor.authorKaper, J.B.
dc.contributor.authorDonowitz, M.
dc.date.accessioned2020-05-18T19:43:56Z
dc.date.available2020-05-18T19:43:56Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85084360909&doi=10.1080%2f19490976.2020.1752125&partnerID=40&md5=d9981be31a643d7f38366ae92b2a424d
dc.identifier.urihttp://hdl.handle.net/10713/12775
dc.description.abstractDiarrhea caused by enterotoxigenic Escherichia coli (ETEC) has a continuing impact on residents and travelers in underdeveloped countries. Both heat-labile (LT) and heat-stable (ST) enterotoxins contribute to pathophysiology via induction of cyclic nucleotide synthesis, and previous investigations focused on intracellular signal transduction rather than possible intercellular second messenger signaling. We modeled ETEC infection in human jejunal enteroid/organoid monolayers (HEM) and evaluated cyclic nucleotide pools, finding that intracellular cAMP was significantly increased but also underwent apical export, whereas cGMP was minimally retained intracellularly and predominantly effluxed into the basolateral space. LT and virulence factors including EatA, EtpA, and CfaE promoted ST release and enhanced ST-stimulated cGMP production. Intracellular cGMP was regulated by MK-571-sensitive export in addition to degradation by phosphodiesterase 5. HEMs had limited ST-induced intracellular cGMP accumulation compared to T84 or Caco-2 models. Cyclic nucleotide export/degradation demonstrates additional complexity in the mechanism of ETEC infection and may redirect understanding of diarrheal onset. Copyright 2020, The Author(s).en_US
dc.description.urihttps://doi.org/10.1080/19490976.2020.1752125en_US
dc.language.isoen_USen_US
dc.publisherTaylor and Francis Inc.en_US
dc.relation.ispartofGut Microbes
dc.subjectcyclic nucleotideen_US
dc.subjectE. coli heat-labile enterotoxinen_US
dc.subjectE. coli heat-stable enterotoxinen_US
dc.subjectenteroid monolayeren_US
dc.subjectETECen_US
dc.subjecthost-pathogen interactionen_US
dc.subjectintestinal organoiden_US
dc.subjectMRP5en_US
dc.subjectPDE5en_US
dc.titlePhosphodiesterase 5 (PDE5) restricts intracellular cGMP accumulation during enterotoxigenic Escherichia coli infectionen_US
dc.typeArticleen_US
dc.identifier.doi10.1080/19490976.2020.1752125
dc.identifier.pmid32378997


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