A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy

Authors

  • Arwa A. Khweek,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Kyle Caution,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Anwari Akhter,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Basant A. Abdulrahman,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
    3. Department of Biochemistry and Molecular Biology Faculty of Pharmacy, Helwan University, Cairo, Egypt
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  • Mia Tazi,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Hoda Hassan,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Neal Majumdar,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Andrew Doran,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Evelyn Guirado,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Larry S. Schlesinger,

    1. Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
    2. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
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  • Howard Shuman,

    1. The University of Chicago, Chicago, IL, USA
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  • Amal O. Amer

    Corresponding author
    1. Department of Internal Medicine, College of Medicine, and The Ohio State University, Columbus, OH, USA
    • Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus, OH, USA
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Full correspondence: Dr. Amal O. Amer, Department of Microbial Infection and Immunity, Center for Microbial Interface Biology and the Department of Internal Medicine, Ohio State University, Biological Research Tower, 460 W 12th Ave, Room 1014, Columbus, OH 43210, USA

Fax: +1-(614)292-9616

e-mail: amal.amer@osumc.edu

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.

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