PMID- 32378997
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20231101
IS  - 1949-0984 (Electronic)
IS  - 1949-0976 (Print)
IS  - 1949-0976 (Linking)
VI  - 12
IP  - 1
DP  - 2020 Nov 9
TI  - Phosphodiesterase 5 (PDE5) restricts intracellular cGMP accumulation during 
      enterotoxigenic Escherichia coli infection.
PG  - 1752125
LID - 10.1080/19490976.2020.1752125 [doi]
LID - 1752125
AB  - Diarrhea 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.
FAU - Foulke-Abel, Jennifer
AU  - Foulke-Abel J
AUID- ORCID: 0000-0003-3882-5625
AD  - Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins 
      University School of Medicine , Baltimore, MD, USA.
FAU - Yu, Huimin
AU  - Yu H
AD  - Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins 
      University School of Medicine , Baltimore, MD, USA.
FAU - Sunuwar, Laxmi
AU  - Sunuwar L
AD  - Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins 
      University School of Medicine , Baltimore, MD, USA.
FAU - Lin, Ruxian
AU  - Lin R
AD  - Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins 
      University School of Medicine , Baltimore, MD, USA.
FAU - Fleckenstein, James M
AU  - Fleckenstein JM
AUID- ORCID: 0000-0002-1148-697X
AD  - Division of Infectious Diseases, Department of Medicine, Washington University 
      School of Medicine , St. Louis, MO, USA.
FAU - Kaper, James B
AU  - Kaper JB
AD  - Department of Microbiology & Immunology, University of Maryland School of 
      Medicine , Baltimore, MD, USA.
FAU - Donowitz, Mark
AU  - Donowitz M
AD  - Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins 
      University School of Medicine , Baltimore, MD, USA.
LA  - eng
GR  - R24 DK099803/DK/NIDDK NIH HHS/United States
GR  - P30 DK089502/DK/NIDDK NIH HHS/United States
GR  - R01 AI126887/AI/NIAID NIH HHS/United States
GR  - P01 AI125181/AI/NIAID NIH HHS/United States
GR  - I01 BX004825/BX/BLRD VA/United States
GR  - T32 DK007632/DK/NIDDK NIH HHS/United States
GR  - U18 TR000552/TR/NCATS NIH HHS/United States
GR  - R01 DK116352/DK/NIDDK NIH HHS/United States
GR  - UH3 TR000504/TR/NCATS NIH HHS/United States
GR  - R01 AI089894/AI/NIAID NIH HHS/United States
GR  - UH3 TR000503/TR/NCATS NIH HHS/United States
GR  - K01 DK113043/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200507
PL  - United States
TA  - Gut Microbes
JT  - Gut microbes
JID - 101495343
RN  - 0 (Bacterial Toxins)
RN  - 0 (CfaE protein, E coli)
RN  - 0 (Enterotoxins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (EtpA protein, E coli)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Propionates)
RN  - 0 (Quinolines)
RN  - 0 (Virulence Factors)
RN  - 0 (heat stable toxin (E coli))
RN  - 147680-16-8 (Fimbriae Proteins)
RN  - 5Q9O54P0H7 (verlukast)
RN  - D9K3SN2LNY (heat-labile enterotoxin, E coli)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
RN  - EC 3.4.- (EatA protein, E coli)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Bacterial Toxins/metabolism
MH  - Caco-2 Cells
MH  - Cell Line, Tumor
MH  - Cyclic GMP/*metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5/*metabolism
MH  - Diarrhea/microbiology/pathology
MH  - Enterotoxigenic Escherichia coli/*metabolism
MH  - Enterotoxins/metabolism
MH  - Epithelial Cells/metabolism
MH  - Escherichia coli Infections/*pathology
MH  - Escherichia coli Proteins/metabolism
MH  - Fimbriae Proteins/metabolism
MH  - Humans
MH  - Jejunum/microbiology/*pathology
MH  - Membrane Glycoproteins/metabolism
MH  - Peptide Hydrolases/metabolism
MH  - Propionates/pharmacology
MH  - Quinolines/pharmacology
MH  - Virulence Factors/metabolism
PMC - PMC7524150
OTO - NOTNLM
OT  - E. coli heat-labile enterotoxin
OT  - E. coli heat-stable enterotoxin
OT  - ETEC
OT  - MRP5
OT  - PDE5
OT  - cyclic nucleotide
OT  - enteroid monolayer
OT  - host-pathogen interaction
OT  - intestinal organoid
EDAT- 2020/05/08 06:00
MHDA- 2021/10/01 06:00
PMCR- 2020/05/07
CRDT- 2020/05/08 06:00
PHST- 2020/05/08 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2020/05/08 06:00 [entrez]
PHST- 2020/05/07 00:00 [pmc-release]
AID - 1752125 [pii]
AID - 10.1080/19490976.2020.1752125 [doi]
PST - ppublish
SO  - Gut Microbes. 2020 Nov 9;12(1):1752125. doi: 10.1080/19490976.2020.1752125. Epub 
      2020 May 7.