Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase

• Published in: Autophagy Vol. 12; no. 11; pp. 2069 - 2084
• Main Authors: Neumann, Yvonne, Bruns, Svenja A., Rohde, Manfred, Prajsnar, Tomasz K., Foster, Simon. J., Schmitz, Ingo
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.11.2016
• Subjects: Animals; ATG5; Autophagosomes - metabolism; Autophagosomes - ultrastructure; Autophagy; Basic Research Paper; Cytosol - metabolism; Enzyme Activation; Green Fluorescent Proteins - metabolism; Host-Pathogen Interactions; Humans; Intracellular Space - microbiology; MAP kinase14; Mice; Mice, Knockout; Microtubule-Associated Proteins - metabolism; Mitogen-Activated Protein Kinase 14 - metabolism; Models, Biological; NIH 3T3 Cells; Protein Binding; S. aureus; selective autophagy; Staphylococcal Infections - enzymology; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus aureus - growth & development; Staphylococcus aureus - physiology; Staphylococcus aureus - ultrastructure; ubiquitin; Ubiquitinated Proteins - metabolism; Ubiquitination; S. aureus; MAP kinase14; ubiquitin; selective autophagy; ATG5
• ISSN: 1554-8627; 1554-8635
• DOI: 10.1080/15548627.2016.1226732

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.