The Brucella effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 32; pp. 1 - 10
• Main Authors: Luizet, Jean-Baptiste, Raymond, Julie, Lacerda, Thais Lourdes Santos, Barbieux, Emeline, Kambarev, Stanimir, Bonici, Magali, Lembo, Frédérique, Willemart, Kévin, Borg, Jean-Paul, Celli, Jean, Gérard, Francine C. A., Muraille, Eric, Gorvel, Jean-Pierre, Salcedo, Suzana P.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 10.08.2021
• Subjects: Animals; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biodegradation; Biological Sciences; Brucella; Brucella abortus - metabolism; Brucella abortus - pathogenicity; Brucellosis - metabolism; Brucellosis - microbiology; Degradation; Egress; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum-Associated Degradation; HeLa Cells; Homeostasis; Host-Pathogen Interactions - physiology; Humans; Infections; Intracellular; Life Sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Pathogens; Perturbation; Protein folding; Protein L; Proteins; Quality control; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Transcription Factor CHOP - genetics; Type IV Secretion Systems - metabolism; Vacuoles; X-Box Binding Protein 1 - genetics; ERAD; Herp; trafficking; Brucella
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2105324118

Perturbation of the endoplasmic reticulum (ER), a central organelle of the cell, can have critical consequences for cellular homeostasis. An elaborate surveillance system known as ER quality control ensures that cells can respond and adapt to stress via the unfolded protein response (UPR) and that only correctly assembled proteins reach their destination. Interestingly, several bacterial pathogens hijack the ER to establish an infection. However, it remains poorly understood how bacterial pathogens exploit ER quality-control functions to complete their intracellular cycle. Brucella spp. replicate extensively within an ER-derived niche, which evolves into specialized vacuoles suited for exit from infected cells. Here we present Brucella-secreted protein L (BspL), a Brucella abortus effector that interacts with Herp, a central component of the ER-associated degradation (ERAD) machinery. We found that BspL enhances ERAD at the late stages of the infection. BspL targeting of Herp and ERAD allows tight control of the kinetics of autophagic Brucella-containing vacuole formation, delaying the last step of its intracellular cycle and cell-to-cell spread. This study highlights a mechanism by which a bacterial pathogen hijacks ERAD components for fine regulation of its intracellular trafficking.