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The Salmonella effector protein SifA plays a dual role in virulence

The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonel...

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Autores principales: Zhao, Weidong, Moest, Thomas, Zhao, Yaya, Guilhon, Aude-Agnès, Buffat, Christophe, Gorvel, Jean-Pierre, Méresse, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534788/
https://www.ncbi.nlm.nih.gov/pubmed/26268777
http://dx.doi.org/10.1038/srep12979
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author Zhao, Weidong
Moest, Thomas
Zhao, Yaya
Guilhon, Aude-Agnès
Buffat, Christophe
Gorvel, Jean-Pierre
Méresse, Stéphane
author_facet Zhao, Weidong
Moest, Thomas
Zhao, Yaya
Guilhon, Aude-Agnès
Buffat, Christophe
Gorvel, Jean-Pierre
Méresse, Stéphane
author_sort Zhao, Weidong
collection PubMed
description The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonella virulence. It is made of two distinct domains. The N-terminal domain of SifA interacts with the host protein SKIP. This interaction regulates vacuolar membrane dynamics. The C-terminal has a fold similar to other bacterial effector domains having a guanine nucleotide exchange factor activity. Although SifA interacts with RhoA, it does not stimulate the dissociation of GDP and the activation of this GTPase. Hence it remains unknown whether the C-terminal domain contributes to the function of SifA in virulence. We used a model of SKIP knockout mice to show that this protein mediates the host susceptibility to salmonellosis and to establish that SifA also contributes to Salmonella virulence independently of its interaction with SKIP. We establish that the C-terminal domain of SifA mediates this SKIP-independent contribution. Moreover, we show that the two domains of SifA are functionally linked and participate to the same signalling cascade that supports Salmonella virulence.
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spelling pubmed-45347882015-08-21 The Salmonella effector protein SifA plays a dual role in virulence Zhao, Weidong Moest, Thomas Zhao, Yaya Guilhon, Aude-Agnès Buffat, Christophe Gorvel, Jean-Pierre Méresse, Stéphane Sci Rep Article The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonella virulence. It is made of two distinct domains. The N-terminal domain of SifA interacts with the host protein SKIP. This interaction regulates vacuolar membrane dynamics. The C-terminal has a fold similar to other bacterial effector domains having a guanine nucleotide exchange factor activity. Although SifA interacts with RhoA, it does not stimulate the dissociation of GDP and the activation of this GTPase. Hence it remains unknown whether the C-terminal domain contributes to the function of SifA in virulence. We used a model of SKIP knockout mice to show that this protein mediates the host susceptibility to salmonellosis and to establish that SifA also contributes to Salmonella virulence independently of its interaction with SKIP. We establish that the C-terminal domain of SifA mediates this SKIP-independent contribution. Moreover, we show that the two domains of SifA are functionally linked and participate to the same signalling cascade that supports Salmonella virulence. Nature Publishing Group 2015-08-13 /pmc/articles/PMC4534788/ /pubmed/26268777 http://dx.doi.org/10.1038/srep12979 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhao, Weidong
Moest, Thomas
Zhao, Yaya
Guilhon, Aude-Agnès
Buffat, Christophe
Gorvel, Jean-Pierre
Méresse, Stéphane
The Salmonella effector protein SifA plays a dual role in virulence
title The Salmonella effector protein SifA plays a dual role in virulence
title_full The Salmonella effector protein SifA plays a dual role in virulence
title_fullStr The Salmonella effector protein SifA plays a dual role in virulence
title_full_unstemmed The Salmonella effector protein SifA plays a dual role in virulence
title_short The Salmonella effector protein SifA plays a dual role in virulence
title_sort salmonella effector protein sifa plays a dual role in virulence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534788/
https://www.ncbi.nlm.nih.gov/pubmed/26268777
http://dx.doi.org/10.1038/srep12979
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