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Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses

Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Understanding the virulence mechanisms of K. pneumoniae is a priority and timely to design new therapeutics. Here, we demonstrate that K. pneumoniae limits the SUMOylation of host proteins in epithelial cells an...

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Autores principales: Sá-Pessoa, Joana, Przybyszewska, Kornelia, Vasconcelos, Filipe Nuno, Dumigan, Amy, Frank, Christian G., Hobley, Laura, Bengoechea, Jose A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527722/
https://www.ncbi.nlm.nih.gov/pubmed/32994335
http://dx.doi.org/10.1128/mBio.01733-20
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author Sá-Pessoa, Joana
Przybyszewska, Kornelia
Vasconcelos, Filipe Nuno
Dumigan, Amy
Frank, Christian G.
Hobley, Laura
Bengoechea, Jose A.
author_facet Sá-Pessoa, Joana
Przybyszewska, Kornelia
Vasconcelos, Filipe Nuno
Dumigan, Amy
Frank, Christian G.
Hobley, Laura
Bengoechea, Jose A.
author_sort Sá-Pessoa, Joana
collection PubMed
description Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Understanding the virulence mechanisms of K. pneumoniae is a priority and timely to design new therapeutics. Here, we demonstrate that K. pneumoniae limits the SUMOylation of host proteins in epithelial cells and macrophages (mouse and human) to subvert cell innate immunity. Mechanistically, in lung epithelial cells, Klebsiella increases the levels of the deSUMOylase SENP2 in the cytosol by affecting its K48 ubiquitylation and its subsequent degradation by the ubiquitin proteasome. This is dependent on Klebsiella preventing the NEDDylation of the Cullin-1 subunit of the ubiquitin ligase complex E3-SCF-βTrCP by exploiting the CSN5 deNEDDylase. Klebsiella induces the expression of CSN5 in an epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-extracellular signal-regulated kinase (ERK)-glycogen synthase kinase 3 beta (GSK3β) signaling pathway-dependent manner. In macrophages, Toll-like receptor 4 (TLR4)-TRAM-TRIF-induced type I interferon (IFN) via IFN receptor 1 (IFNAR1)-controlled signaling mediates Klebsiella-triggered decrease in the levels of SUMOylation via let-7 microRNAs (miRNAs). Our results revealed the crucial role played by Klebsiella polysaccharides, the capsule, and the lipopolysaccharide (LPS) O-polysaccharide, to decrease the levels of SUMO-conjugated proteins in epithelial cells and macrophages. A Klebsiella-induced decrease in SUMOylation promotes infection by limiting the activation of inflammatory responses and increasing intracellular survival in macrophages.
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spelling pubmed-75277222020-10-19 Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses Sá-Pessoa, Joana Przybyszewska, Kornelia Vasconcelos, Filipe Nuno Dumigan, Amy Frank, Christian G. Hobley, Laura Bengoechea, Jose A. mBio Research Article Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Understanding the virulence mechanisms of K. pneumoniae is a priority and timely to design new therapeutics. Here, we demonstrate that K. pneumoniae limits the SUMOylation of host proteins in epithelial cells and macrophages (mouse and human) to subvert cell innate immunity. Mechanistically, in lung epithelial cells, Klebsiella increases the levels of the deSUMOylase SENP2 in the cytosol by affecting its K48 ubiquitylation and its subsequent degradation by the ubiquitin proteasome. This is dependent on Klebsiella preventing the NEDDylation of the Cullin-1 subunit of the ubiquitin ligase complex E3-SCF-βTrCP by exploiting the CSN5 deNEDDylase. Klebsiella induces the expression of CSN5 in an epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-extracellular signal-regulated kinase (ERK)-glycogen synthase kinase 3 beta (GSK3β) signaling pathway-dependent manner. In macrophages, Toll-like receptor 4 (TLR4)-TRAM-TRIF-induced type I interferon (IFN) via IFN receptor 1 (IFNAR1)-controlled signaling mediates Klebsiella-triggered decrease in the levels of SUMOylation via let-7 microRNAs (miRNAs). Our results revealed the crucial role played by Klebsiella polysaccharides, the capsule, and the lipopolysaccharide (LPS) O-polysaccharide, to decrease the levels of SUMO-conjugated proteins in epithelial cells and macrophages. A Klebsiella-induced decrease in SUMOylation promotes infection by limiting the activation of inflammatory responses and increasing intracellular survival in macrophages. American Society for Microbiology 2020-09-29 /pmc/articles/PMC7527722/ /pubmed/32994335 http://dx.doi.org/10.1128/mBio.01733-20 Text en Copyright © 2020 Sá-Pessoa et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Sá-Pessoa, Joana
Przybyszewska, Kornelia
Vasconcelos, Filipe Nuno
Dumigan, Amy
Frank, Christian G.
Hobley, Laura
Bengoechea, Jose A.
Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses
title Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses
title_full Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses
title_fullStr Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses
title_full_unstemmed Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses
title_short Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses
title_sort klebsiella pneumoniae reduces sumoylation to limit host defense responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527722/
https://www.ncbi.nlm.nih.gov/pubmed/32994335
http://dx.doi.org/10.1128/mBio.01733-20
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