A Role for the VPS Retromer in Brucella Intracellular Replication Revealed by Genomewide siRNA Screening

• DOI: 10.1128/msphere.00380-19
• Publication Date: 2019-06-25T11:48:59Z
• Authors: Alain Casanova; Shyan Huey Low; Maxime Québatte; Jaroslaw Sedzicki; Therese Tschon; Maren Ketterer; Kevin Smith; Mario Emmenlauer; Houchaima Ben-Tekaya; Christoph Dehio
• Keywords: DNA Replication; 0301 basic medicine; replicative niche; Cellbiologi; Brucella abortus; Endoplasmic Reticulum; Microbiology; 03 medical and health sciences; Humans; :Medicine [Science]; RNA, Small Interfering; VPS35; Endosomal Sorting Complexes Required for Transport; RAB7A; Cell Biology; Brucella; QR1-502; High-Throughput Screening Assays; 3. Good health; VPS retromer; siRNA; Gene Knockdown Techniques; Host-Pathogen Interactions; Vacuoles; VPS26; Genome, Bacterial; Research Article; HeLa Cells

With >300,000 new cases of human brucellosis annually, Brucella is regarded as one of the most important zoonotic bacterial pathogens worldwide. The agent causing brucellosis resides inside host cells within vacuoles termed Brucella- containing vacuoles (BCVs). Although a few host components required to escape the degradative lysosomal pathway and to establish the ER-derived replicative BCV (rBCV) have already been identified, the global understanding of this highly coordinated process is still partial, and many factors remain unknown. To gain deeper insight into these fundamental questions, we performed a genomewide RNA interference (RNAi) screen aiming at discovering novel host factors involved in the Brucella intracellular cycle. We identified 425 host proteins that contribute to Brucella cellular entry, intracellular trafficking, and replication. Together, this study sheds light on previously unknown host pathways required for the Brucella infection cycle and highlights the VPS retromer components as critical factors for the establishment of the Brucella intracellular replicative niche.