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

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 o...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2021-08, Vol.118 (32), p.1
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: Article
Language:English
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
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Summary: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. spp. replicate extensively within an ER-derived niche, which evolves into specialized vacuoles suited for exit from infected cells. Here we present secreted protein L (BspL), a 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 -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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2105324118