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Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum
The intracellular pathogen Brucella is the causative agent of brucellosis, a worldwide zoonosis that affects mammals, including humans. Essential to Brucella virulence is its ability to survive and replicate inside host macrophages, yet the underlying mechanisms and the nature of the replicative com...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194179/ https://www.ncbi.nlm.nih.gov/pubmed/12925673 http://dx.doi.org/10.1084/jem.20030088 |
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author | Celli, Jean de Chastellier, Chantal Franchini, Don-Marc Pizarro-Cerda, Javier Moreno, Edgardo Gorvel, Jean-Pierre |
author_facet | Celli, Jean de Chastellier, Chantal Franchini, Don-Marc Pizarro-Cerda, Javier Moreno, Edgardo Gorvel, Jean-Pierre |
author_sort | Celli, Jean |
collection | PubMed |
description | The intracellular pathogen Brucella is the causative agent of brucellosis, a worldwide zoonosis that affects mammals, including humans. Essential to Brucella virulence is its ability to survive and replicate inside host macrophages, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here we show in a model of Brucella abortus infection of murine bone marrow–derived macrophages that a fraction of the bacteria that survive an initial macrophage killing proceed to replicate in a compartment segregated from the endocytic pathway. The maturation of the Brucella-containing vacuole involves sustained interactions and fusion with the endoplasmic reticulum (ER), which creates a replicative compartment with ER-like properties. The acquisition of ER membranes by replicating Brucella is independent of ER-Golgi COPI-dependent vesicular transport. A mutant of the VirB type IV secretion system, which is necessary for intracellular survival, was unable to sustain interactions and fuse with the ER, and was killed via eventual fusion with lysosomes. Thus, we demonstrate that live intracellular Brucella evade macrophage killing through VirB-dependent sustained interactions with the ER. Moreover, we assign an intracellular function to the VirB system, as being required for late maturation events necessary for the biogenesis of an ER-derived replicative organelle. |
format | Text |
id | pubmed-2194179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21941792008-04-11 Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum Celli, Jean de Chastellier, Chantal Franchini, Don-Marc Pizarro-Cerda, Javier Moreno, Edgardo Gorvel, Jean-Pierre J Exp Med Article The intracellular pathogen Brucella is the causative agent of brucellosis, a worldwide zoonosis that affects mammals, including humans. Essential to Brucella virulence is its ability to survive and replicate inside host macrophages, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here we show in a model of Brucella abortus infection of murine bone marrow–derived macrophages that a fraction of the bacteria that survive an initial macrophage killing proceed to replicate in a compartment segregated from the endocytic pathway. The maturation of the Brucella-containing vacuole involves sustained interactions and fusion with the endoplasmic reticulum (ER), which creates a replicative compartment with ER-like properties. The acquisition of ER membranes by replicating Brucella is independent of ER-Golgi COPI-dependent vesicular transport. A mutant of the VirB type IV secretion system, which is necessary for intracellular survival, was unable to sustain interactions and fuse with the ER, and was killed via eventual fusion with lysosomes. Thus, we demonstrate that live intracellular Brucella evade macrophage killing through VirB-dependent sustained interactions with the ER. Moreover, we assign an intracellular function to the VirB system, as being required for late maturation events necessary for the biogenesis of an ER-derived replicative organelle. The Rockefeller University Press 2003-08-18 /pmc/articles/PMC2194179/ /pubmed/12925673 http://dx.doi.org/10.1084/jem.20030088 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Celli, Jean de Chastellier, Chantal Franchini, Don-Marc Pizarro-Cerda, Javier Moreno, Edgardo Gorvel, Jean-Pierre Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum |
title |
Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum |
title_full |
Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum |
title_fullStr |
Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum |
title_full_unstemmed |
Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum |
title_short |
Brucella Evades Macrophage Killing via VirB-dependent Sustained Interactions with the Endoplasmic Reticulum |
title_sort | brucella evades macrophage killing via virb-dependent sustained interactions with the endoplasmic reticulum |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194179/ https://www.ncbi.nlm.nih.gov/pubmed/12925673 http://dx.doi.org/10.1084/jem.20030088 |
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