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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5679646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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