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Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication

Salmonella enterica serovar typhimurium extensively remodels the host late endocytic compartments to establish its vacuolar niche within the host cells conducive for its replication, also known as the Salmonella-containing vacuole (SCV). By maintaining a prolonged interaction with late endosomes and...

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Autores principales: Sindhwani, Aastha, Arya, Subhash B., Kaur, Harmeet, Jagga, Divya, Tuli, Amit, Sharma, Mahak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679646/
https://www.ncbi.nlm.nih.gov/pubmed/29084291
http://dx.doi.org/10.1371/journal.ppat.1006700
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author Sindhwani, Aastha
Arya, Subhash B.
Kaur, Harmeet
Jagga, Divya
Tuli, Amit
Sharma, Mahak
author_facet Sindhwani, Aastha
Arya, Subhash B.
Kaur, Harmeet
Jagga, Divya
Tuli, Amit
Sharma, Mahak
author_sort Sindhwani, Aastha
collection PubMed
description Salmonella enterica serovar typhimurium extensively remodels the host late endocytic compartments to establish its vacuolar niche within the host cells conducive for its replication, also known as the Salmonella-containing vacuole (SCV). By maintaining a prolonged interaction with late endosomes and lysosomes of the host cells in the form of interconnected network of tubules (Salmonella-induced filaments or SIFs), Salmonella gains access to both membrane and fluid-phase cargo from these compartments. This is essential for maintaining SCV membrane integrity and for bacterial intravacuolar nutrition. Here, we have identified the multisubunit lysosomal tethering factor—HOPS (HOmotypic fusion and Protein Sorting) complex as a crucial host factor facilitating delivery of late endosomal and lysosomal content to SCVs, providing membrane for SIF formation, and nutrients for intravacuolar bacterial replication. Accordingly, depletion of HOPS subunits significantly reduced the bacterial load in non-phagocytic and phagocytic cells as well as in a mouse model of Salmonella infection. We found that Salmonella effector SifA in complex with its binding partner; SKIP, interacts with HOPS subunit Vps39 and mediates recruitment of this tethering factor to SCV compartments. The lysosomal small GTPase Arl8b that binds to, and promotes membrane localization of Vps41 (and other HOPS subunits) was also required for HOPS recruitment to SCVs and SIFs. Our findings suggest that Salmonella recruits the host late endosomal and lysosomal membrane fusion machinery to its vacuolar niche for access to host membrane and nutrients, ensuring its intracellular survival and replication.
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spelling pubmed-56796462017-11-18 Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication Sindhwani, Aastha Arya, Subhash B. Kaur, Harmeet Jagga, Divya Tuli, Amit Sharma, Mahak PLoS Pathog Research Article Salmonella enterica serovar typhimurium extensively remodels the host late endocytic compartments to establish its vacuolar niche within the host cells conducive for its replication, also known as the Salmonella-containing vacuole (SCV). By maintaining a prolonged interaction with late endosomes and lysosomes of the host cells in the form of interconnected network of tubules (Salmonella-induced filaments or SIFs), Salmonella gains access to both membrane and fluid-phase cargo from these compartments. This is essential for maintaining SCV membrane integrity and for bacterial intravacuolar nutrition. Here, we have identified the multisubunit lysosomal tethering factor—HOPS (HOmotypic fusion and Protein Sorting) complex as a crucial host factor facilitating delivery of late endosomal and lysosomal content to SCVs, providing membrane for SIF formation, and nutrients for intravacuolar bacterial replication. Accordingly, depletion of HOPS subunits significantly reduced the bacterial load in non-phagocytic and phagocytic cells as well as in a mouse model of Salmonella infection. We found that Salmonella effector SifA in complex with its binding partner; SKIP, interacts with HOPS subunit Vps39 and mediates recruitment of this tethering factor to SCV compartments. The lysosomal small GTPase Arl8b that binds to, and promotes membrane localization of Vps41 (and other HOPS subunits) was also required for HOPS recruitment to SCVs and SIFs. Our findings suggest that Salmonella recruits the host late endosomal and lysosomal membrane fusion machinery to its vacuolar niche for access to host membrane and nutrients, ensuring its intracellular survival and replication. Public Library of Science 2017-10-30 /pmc/articles/PMC5679646/ /pubmed/29084291 http://dx.doi.org/10.1371/journal.ppat.1006700 Text en © 2017 Sindhwani et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sindhwani, Aastha
Arya, Subhash B.
Kaur, Harmeet
Jagga, Divya
Tuli, Amit
Sharma, Mahak
Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication
title Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication
title_full Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication
title_fullStr Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication
title_full_unstemmed Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication
title_short Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication
title_sort salmonella exploits the host endolysosomal tethering factor hops complex to promote its intravacuolar replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679646/
https://www.ncbi.nlm.nih.gov/pubmed/29084291
http://dx.doi.org/10.1371/journal.ppat.1006700
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