title: A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy.
abstract: Legionella pneumophila (L. pneumophila) is an intracellular bacterium of human alveolar macrophages that causes Legionnaires' disease. In contrast to humans, most inbred mouse strains are restrictive to L. pneumophila replication. We demonstrate that autophagy targets L. pneumophila vacuoles to lysosomes and that this process requires ubiquitination of L. pneumophila vacuoles and the subsequent binding of the autophagic adaptor p62/SQSTM1 to ubiquitinated vacuoles. The L. pneumophila legA9 encodes for an ankyrin-containing protein with unknown role. We show that the legA9 mutant replicate in WT mice and their bone marrow-derived macrophages. This is the first L. pneumophila mutant to be found to replicate in WT bone marrow-derived macrophages other than the Fla mutant. Less legA9 mutant-containing vacuoles acquired ubiquitin labeling and p62/SQSTM1 staining, evading autophagy uptake and avoiding lysosomal fusion. Thus, we describe a bacterial protein that targets the L. pneumophila-containing vacuole for autophagy uptake.
authors: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH 43210, USA.
authors: Arwa A
authors: AA
authors: Khweek
authors: Kyle
authors: K
authors: Caution
authors: Anwari
authors: A
authors: Akhter
authors: Basant A
authors: BA
authors: Abdulrahman
authors: Mia
authors: M
authors: Tazi
authors: Hoda
authors: H
authors: Hassan
authors: Neal
authors: N
authors: Majumdar
authors: Andrew
authors: A
authors: Doran
authors: Evelyn
authors: E
authors: Guirado
authors: Larry S
authors: LS
authors: Schlesinger
authors: Howard
authors: H
authors: Shuman
authors: Amal O
authors: AO
authors: Amer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D001343:Autophagy / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D016952:Legionella pneumophila / Q000235:genetics* / Q000276:immunology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D009154:Mutation; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D014617:Vacuoles / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D025801:Ubiquitin