title: Recruitment of TBK1 to cytosol-invading Salmonella induces WIPI2-dependent antibacterial autophagy.
abstract: Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti-bacterial autophagy relies on the core autophagy machinery, cargo receptors, and "eat-me" signals such as galectin-8 and ubiquitin that label bacteria as autophagy cargo. Anti-bacterial autophagy also requires the kinase TBK1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti-bacterial autophagy, is dependent on the localization of catalytically active TBK1 to the vicinity of cytosolic bacteria. Experimental manipulation of TBK1 recruitment revealed that engagement of TBK1 with any of a variety of Salmonella-associated "eat-me" signals, including host-derived glycans and K48- and K63-linked ubiquitin chains, suffices to restrict bacterial proliferation. Promiscuity in recruiting TBK1 via independent signals may buffer TBK1 functionality from potential bacterial antagonism and thus be of evolutionary advantage to the host.
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
authors.forename: Teresa Lm
authors.initials: TL
authors.lastname: Thurston
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Keith B
authors.initials: KB
authors.lastname: Boyle
authors.affiliation: Division of Structural Studies, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Allen
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Ravenhill
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Maryia
authors.initials: M
authors.lastname: Karpiyevich
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Bloor
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Annie
authors.identifier: 0000-0002-9965-8026
authors.initials: A
authors.lastname: Kaul
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Noad
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Agnes
authors.initials: A
authors.lastname: Foeglein
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Matthews
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Komander
authors.affiliation: Division of Structural Studies, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bycroft
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK randow@mrc-lmb.cam.ac.uk.
authors.forename: Felix
authors.identifier: 0000-0003-0694-5315
authors.initials: F
authors.lastname: Randow
mesh_terms: D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism*; D003600:Cytosol / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D028044:Phosphate-Binding Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D028044:Phosphate-Binding Proteins; C569007:WIPI2 protein, human; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human
keywords: PI(3)P; Salmonella; TBK1; WIPI; anti‐bacterial autophagy