title: Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle.
abstract: Autophagy is a cellular degradation process that can capture and eliminate intracellular microbes by delivering them to lysosomes for destruction. However, pathogens have evolved mechanisms to subvert this process. The intracellular bacterium Brucella abortus ensures its survival by forming the Brucella-containing vacuole (BCV), which traffics from the endocytic compartment to the endoplasmic reticulum (ER), where the bacterium proliferates. We show that Brucella replication in the ER is followed by BCV conversion into a compartment with autophagic features (aBCV). While Brucella trafficking to the ER was unaffected in autophagy-deficient cells, aBCV formation required the autophagy-initiation proteins ULK1, Beclin 1, and ATG14L and PI3-kinase activity. However, aBCV formation was independent of the autophagy-elongation proteins ATG5, ATG16L1, ATG4B, ATG7, and LC3B. Furthermore, aBCVs were required to complete the intracellular Brucella lifecycle and for cell-to-cell spreading, demonstrating that Brucella selectively co-opts autophagy-initiation complexes to subvert host clearance and promote infection.
authors.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Tregei
authors.initials: T
authors.lastname: Starr
authors.forename: Robert
authors.initials: R
authors.lastname: Child
authors.forename: Tara D
authors.initials: TD
authors.lastname: Wehrly
authors.forename: Bryan
authors.initials: B
authors.lastname: Hansen
authors.forename: Seungmin
authors.initials: S
authors.lastname: Hwang
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otin
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
authors.forename: Jean
authors.initials: J
authors.lastname: Celli
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D002460:Cell Line; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D057131:Immune Evasion; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*