title: Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase.
abstract: Autophagy, a catabolic pathway of lysosomal degradation, acts not only as an efficient recycle and survival mechanism during cellular stress, but also as an anti-infective machinery. The human pathogen Staphylococcus aureus (S. aureus) was originally considered solely as an extracellular bacterium, but is now recognized additionally to invade host cells, which might be crucial for persistence. However, the intracellular fate of S. aureus is incompletely understood. Here, we show for the first time induction of selective autophagy by S. aureus infection, its escape from autophagosomes and proliferation in the cytoplasm using live cell imaging. After invasion, S. aureus becomes ubiquitinated and recognized by receptor proteins such as SQSTM1/p62 leading to phagophore recruitment. Yet, S. aureus evades phagophores and prevents further degradation by a MAPK14/p38α MAP kinase-mediated blockade of autophagy. Our study demonstrates a novel bacterial strategy to block autophagy and secure survival inside the host cell.
authors.affiliation: a Institute of Molecular and Clinical Immunology , Otto-von-Guericke-University Magdeburg , Magdeburg , Germany.|b Systems-oriented Immunology and Inflammation Research Group, Department of Immune Control , Helmholtz Centre for Infection Research , Braunschweig , Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Neumann
authors.affiliation: a Institute of Molecular and Clinical Immunology , Otto-von-Guericke-University Magdeburg , Magdeburg , Germany.|b Systems-oriented Immunology and Inflammation Research Group, Department of Immune Control , Helmholtz Centre for Infection Research , Braunschweig , Germany.
authors.forename: Svenja A
authors.initials: SA
authors.lastname: Bruns
authors.affiliation: c Central Facility for Microscopy, Department of Molecular Infection Biology , Helmholtz Centre for Infection Research , Braunschweig , Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: d Krebs Institute, Department of Molecular Biology and Biotechnology , University of Sheffield, Western Bank , Sheffield , UK.
authors.forename: Tomasz K
authors.initials: TK
authors.lastname: Prajsnar
authors.affiliation: d Krebs Institute, Department of Molecular Biology and Biotechnology , University of Sheffield, Western Bank , Sheffield , UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
authors.affiliation: a Institute of Molecular and Clinical Immunology , Otto-von-Guericke-University Magdeburg , Magdeburg , Germany.|b Systems-oriented Immunology and Inflammation Research Group, Department of Immune Control , Helmholtz Centre for Infection Research , Braunschweig , Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Schmitz
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism / Q000648:ultrastructure; D001343:Autophagy; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D008954:Models, Biological; D041681:NIH 3T3 Cells; D011485:Protein Binding; D013203:Staphylococcal Infections / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D057149:Ubiquitinated Proteins; D049452:Green Fluorescent Proteins; D048308:Mitogen-Activated Protein Kinase 14
keywords: ATG5; MAP kinase14; S. aureus; selective autophagy; ubiquitin