Novel pathomechanism for spontaneous bacterial peritonitis: disruption of cell junctions by cellular and bacterial proteases.
Ascites
/ microbiology
Bacterial Translocation
/ physiology
Caco-2 Cells
Cadherins
/ metabolism
Case-Control Studies
Coculture Techniques
Colon
/ microbiology
Escherichia coli
/ physiology
Female
Humans
Intercellular Junctions
Liver Cirrhosis
/ complications
Male
Occludin
/ metabolism
Peptide Hydrolases
Peritonitis
/ etiology
Proteus mirabilis
/ physiology
E. coli
bacterial translocation
liver cirrhosis
peritonitis
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
01
05
2020
revised:
17
02
2021
accepted:
24
02
2021
pubmed:
13
3
2021
medline:
9
3
2022
entrez:
12
3
2021
Statut:
ppublish
Résumé
Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis with a 1-year mortality of 66%. Bacterial translocation (BT) from the intestine to the mesenteric lymph nodes is crucial for the pathogenesis of SBP. Since BT presupposes a leaky intestinal epithelium, the integrity of mucus and epithelial cell junctions (E-cadherin and occludin) was examined in colonic biopsies from patients with liver cirrhosis and controls. SBP-inducing SBP-derived Patients with liver cirrhosis show a reduced thickness of colonic mucus, which allows bacteria-to-epithelial cell contact. Intestinal bacteria induce degradation of occludin by exploiting the proteasome of epithelial cells. We identified a novel bacterial protease activity of patient-derived SBP-inducing bacteria, which is responsible for the cleavage of E-cadherin structures. Inhibition of this protease activity leads to stabilisation of cell junctions. Thus, targeting these mechanisms by blocking the ubiquitin-proteasome system and/or the bacterial protease activity might interfere with BT and constitute a novel innovative therapeutic strategy to prevent SBP in patients with liver cirrhosis.
Identifiants
pubmed: 33707230
pii: gutjnl-2020-321663
doi: 10.1136/gutjnl-2020-321663
pmc: PMC8862089
doi:
Substances chimiques
Cadherins
0
Occludin
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
580-592Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: MM and CK report grants from Federal Ministry for Economic Affairs and Energy (Germany) during the conduct of the study.
Références
Nat Rev Gastroenterol Hepatol. 2017 Dec;14(12):697-710
pubmed: 28930292
Drug Des Devel Ther. 2020 Oct 19;14:4327-4342
pubmed: 33116419
Gut. 2014 Feb;63(2):281-91
pubmed: 23426893
Gut. 2021 May;70(5):982-994
pubmed: 33060124
Pharmacol Res. 2021 Jan;163:105248
pubmed: 33065283
Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):352-61
pubmed: 23478383
Hepatology. 2011 Aug;54(2):562-72
pubmed: 21574172
Cell Tissue Res. 2018 Dec;374(3):455-463
pubmed: 30218241
Immunol Rev. 2014 Jul;260(1):8-20
pubmed: 24942678
Nat Rev Drug Discov. 2011 Jan;10(1):29-46
pubmed: 21151032
Gut. 2016 Jul;65(7):1215-24
pubmed: 27196587
Science. 2015 Nov 13;350(6262):830-4
pubmed: 26564856
Science. 2002 Mar 1;295(5560):1726-9
pubmed: 11872843
Med Res Rev. 2018 Jul;38(4):1295-1331
pubmed: 29149530
J Hepatol. 2018 Aug;69(2):406-460
pubmed: 29653741
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15064-9
pubmed: 18806221
Gastroenterology. 1989 Mar;96(3):736-49
pubmed: 2914637
Cell Physiol Biochem. 2005;15(1-4):29-40
pubmed: 15665513
Nat Rev Gastroenterol Hepatol. 2018 Jul;15(7):397-411
pubmed: 29748586
Gut. 2016 May;65(5):749-56
pubmed: 26719299
J Biol Chem. 2011 Jan 7;286(1):441-9
pubmed: 20980253
J Vis Exp. 2010 Nov 08;(45):
pubmed: 21085107
Front Cell Dev Biol. 2020 Oct 26;8:582361
pubmed: 33195227
Liver Int. 2015 Sep;35(9):2121-8
pubmed: 25644943
Gastroenterology. 2020 Sep;159(3):849-863
pubmed: 32569766
J Hepatol. 2020 Mar;72(3):558-577
pubmed: 31622696
Cell Res. 2016 Apr;26(4):499-510
pubmed: 26964724
Gastroenterology. 2019 Apr;156(5):1368-1380.e10
pubmed: 30552895
Clin Cancer Res. 1999 Mar;5(3):513-20
pubmed: 10100701
J Cell Sci. 2017 Jun 15;130(12):1985-1996
pubmed: 28476939
Gut. 2018 Oct;67(10):1870-1880
pubmed: 28847867
J Hepatol. 2019 Mar;70(3):398-411
pubmed: 30391380
J Hepatol. 2014 Jan;60(1):197-209
pubmed: 23993913
Gut. 2019 Dec;68(12):2142-2151
pubmed: 30914450
Gut. 2018 Sep;67(9):1716-1725
pubmed: 29934437
Tissue Barriers. 2013 Apr 1;1(2):e24783
pubmed: 24665393
Gut. 2007 Mar;56(3):343-50
pubmed: 16908512
Nature. 2002 Apr 18;416(6882):703-9
pubmed: 11961546
J Hepatol. 2019 Dec;71(6):1126-1140
pubmed: 31295531
Gastroenterology. 2006 Jul;131(1):117-29
pubmed: 16831596
Nat Rev Immunol. 2021 Mar;21(3):137-150
pubmed: 32782357
Science. 2020 Oct 23;370(6515):402-403
pubmed: 33093095
J Hepatol. 2001 Jan;34(1):150-5
pubmed: 11211893
Mol Cell Biol. 2012 Jan;32(2):242-50
pubmed: 22083955
Eur J Clin Invest. 2012 Apr;42(4):439-46
pubmed: 22023490
J Hepatol. 2017 Nov;67(5):1084-1103
pubmed: 28526488
Tissue Cell. 2011 Jun;43(3):201-6
pubmed: 21470648
Hepatol Res. 2020 Feb;50(2):233-245
pubmed: 31667938
Gut. 2021 Jan;70(1):9-29
pubmed: 33067334
Gut. 2020 Dec;69(12):2232-2243
pubmed: 32917747
Hepat Med. 2019 Jan 14;11:13-22
pubmed: 30666172
J Gastroenterol. 2018 Jan;53(1):27-36
pubmed: 28770351