Inactivation of Rho GTPases by Burkholderia cenocepacia Induces a WASH-Mediated Actin Polymerization that Delays Phagosome Maturation
| Autor: | Joshua Piotrowski, Brandon Tang, Glenn F. W. Walpole, Valentin Jaumouillé, Sergio Grinstein, Daniel D. Billadeau, Benoit Boulay, Jonathan Plumb, Daniel Chung, Sergio D. Catz, Douglas G. Osborne |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male rho GTP-Binding Proteins Burkholderia cenocepacia Bacterial Toxins Vesicular Transport Proteins Bone Marrow Cells Vacuole macromolecular substances General Biochemistry Genetics and Molecular Biology Article Actin-Related Protein 2-3 Complex 03 medical and health sciences Mice WASH 0302 clinical medicine Phagosomes Phagosome maturation Macrophage Animals lcsh:QH301-705.5 Actin Phagosome Mice Knockout biology Clostridioides difficile Effector Chemistry Macrophages Rho GTPase Microfilament Proteins phagocytosis Cortical actin cytoskeleton biology.organism_classification Cell biology Mice Inbred C57BL Actin Cytoskeleton 030104 developmental biology RAW 264.7 Cells lcsh:Biology (General) Female Arp2/3 Lysosomes 030217 neurology & neurosurgery |
| Zdroj: | Cell reports Cell Reports, Vol 31, Iss 9, Pp-(2020) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Burkholderia cenocepacia is an opportunistic bacterial pathogen that causes severe pulmonary infections in cystic fibrosis and chronic granulomatous disease patients. B. cenocepacia can survive inside infected macrophages within the B. cenocepacia-containing vacuole (BcCV) and to elicit a severe inflammatory response. By inactivating the host macrophage Rho GTPases, the bacterial effector TecA causes depolymerization of the cortical actin cytoskeleton. In this study, we find that B. cenocepacia induces the formation of large cytosolic F-actin clusters in infected macrophages. Cluster formation requires the nucleation-promoting factor WASH, the Arp2/3 complex, and TecA. Inactivation of Rho GTPases by bacterial toxins is necessary and sufficient to induce the formation of the cytosolic actin clusters. By hijacking WASH and Arp2/3 activity, B. cenocepacia disrupts interactions with the endolysosomal system, thereby delaying the maturation of the BcCV. In Brief Despite causing profound inhibition of host cell Rho GTPases, Burkholderia cenocepacia induces F-actin polymerization near endomembranes, particularly around phagosomes. Walpole et al. show that WASH, an Arp2/3 activator, is required for this de novo F-actin polymerization. The F-actin clusters formed around phagosomes delay their maturation, preventing their fusion with lysosomes. Graphical Abstract |
| Databáze: | OpenAIRE |
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