title: Brucella coopts the small GTPase Sar1 for intracellular replication.
abstract: The pathogen Brucella abortus resides inside macrophages within a unique, replication-permissive organelle that is derived from the endoplasmic reticulum (ER). Although dependent on the Brucella type IV secretion system VirB, the mechanisms governing the biogenesis of this compartment remain elusive. Here, we investigated a putative role of the early secretory pathway in ER membrane accretion by the Brucella-containing vacuoles (BCVs). We show that BCVs interact with ER exit sites (ERES), and blockade of Sar1 activity, which disrupts ERES, prevents intracellular replication of Brucella. In cells expressing the dominant interfering form Sar1[T39N], BCVs do not acquire ER membranes, suggesting that they are unable to mature into replicative organelles. By contrast, treatments that block subsequent secretory events do not affect bacterial replication. We propose that Sar1-dependent ERES functions, but not subsequent secretory events, are essential for the biogenesis of the Brucella replicative compartment and, thus, bacterial replication. These results assign an essential role for Sar1 in pathogenesis of an intracellular bacterium.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université delaMéditerranée, 13288 Marseille Cedex 09, France. jcelli@niaid.nih.gov
authors.forename: Jean
authors.initials: J
authors.lastname: Celli
authors.forename: Suzana P
authors.initials: SP
authors.lastname: Salcedo
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000382:microbiology; D002003:Brucella abortus / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000502:physiology / Q000648:ultrastructure
chemical_list: C493083:SAR1A protein, human; C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins