Inactivation of Rho GTPases by Burkholderia cenocepacia Induces a WASH-Mediated Actin Polymerization that Delays Phagosome Maturation

Glenn F.W. Walpole, Jonathan D. Plumb, Daniel Chung, Brandon Tang, Benoit Boulay, Douglas G. Osborne, Joshua T. Piotrowski, Sergio D. Catz, Daniel D. Billadeau, Sergio Grinstein, Valentin Jaumouillé

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number107721
JournalCell reports
Volume31
Issue number9
DOIs
StatePublished - Jun 2 2020

Keywords

  • Arp2/3
  • Burkholderia cenocepacia
  • Clostridioides difficile
  • Rho GTPase
  • WASH
  • host-pathogen
  • macrophage
  • phagocytosis
  • phagosome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Walpole, G. F. W., Plumb, J. D., Chung, D., Tang, B., Boulay, B., Osborne, D. G., Piotrowski, J. T., Catz, S. D., Billadeau, D. D., Grinstein, S., & Jaumouillé, V. (2020). Inactivation of Rho GTPases by Burkholderia cenocepacia Induces a WASH-Mediated Actin Polymerization that Delays Phagosome Maturation. Cell reports, 31(9), [107721]. https://doi.org/10.1016/j.celrep.2020.107721