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

Walpole, GFW;Plumb, JD;Chung, D;Tang, B;Boulay, B;Osborne, DG;Piotrowski, JT;Catz, SD;Billadeau, DD;Grinstein, S;Jaumouill, V;

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. Copyright 2020 The Author(s). Published by Elsevier Inc. All rights reserved.