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Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase
Authors:Yvonne Neumann  Svenja A Bruns  Manfred Rohde  Tomasz K Prajsnar  Simon J Foster
Institution:1. Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany;2. Systems-oriented Immunology and Inflammation Research Group, Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany;3. Central Facility for Microscopy, Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany;4. Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, UK
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.
Keywords:ATG5  MAP kinase14  S  aureus  selective autophagy  ubiquitin
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