Enviado por Alexis Mendoza-León
Nicolas Personnic, Kevin Bärlocher, Ivo Finsel, Hubert Hilbi
Publication stage: In Press Corrected Proof
Intracellular bacterial pathogens subvert the endocytic bactericidal pathway to form specific replication-permissive compartments termed pathogen vacuoles or inclusions. To this end, the pathogens employ type III or type IV secretion systems, which translocate dozens, if not hundreds, of different effector proteins into their host cells, where they manipulate vesicle trafficking and signaling pathways in favor of the intruders. While the distinct cocktail of effectors defines the specific processes by which a pathogen vacuole is formed, the different pathogens commonly target certain vesicle trafficking routes, including the endocytic or secretory pathway. Recently, the retrograde transport pathway from endosomal compartments to the trans-Golgi network emerged as an important route affecting pathogen vacuole formation. Here, we review current insight into the host cell’s retrograde trafficking pathway and how vacuolar pathogens of the genera Legionella, Coxiella, Salmonella,Chlamydia, and Simkania employ mechanistically distinct strategies to subvert this pathway, thus promoting intracellular survival and replication.
Intracellular bacterial pathogens translocate various effector proteins into host cells, where they modulate membrane dynamics and vesicle trafficking in order to establish a replicative niche termed the pathogen-containing vacuole.
The retrograde vesicle trafficking pathway promotes transport from early, late, and recycling endosomes to the trans-Golgi network (TGN) and back to the endoplasmic reticulum (ER). Key components of this pathway are the COPI and retromer coats, sorting nexin (SNX) proteins, and phosphoinositide (PI) lipids, as well as the PI 5-phosphatase OCRL and small GTPases of the Rab family (Rab5, Rab7, and Rab9).
Bacterial effector proteins blocking retrograde transport are (i) Legionella pneumophila RidL, which binds to the retromer, (ii) Salmonella Typhimurium SifA, which interacts with SKIP/kinesin, and (iii) Chlamydia trachomatis IncE, which binds to SNX5/6.