A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy. Issue 5 (8th April 2013)

• Record Type: Journal Article
• Authors: Khweek, Arwa A.; Caution, Kyle; Akhter, Anwari; Abdulrahman, Basant A.; Tazi, Mia; Hassan, Hoda; Majumdar, Neal; Doran, Andrew; Guirado, Evelyn; Schlesinger, Larry S.; Shuman, Howard; Amer, Amal O.
• Is Part Of: European journal of immunology. Volume 43:Issue 5(2013:May)
• Page Start: 1333
• Page End: 1344
• Publication Date: 2013-04-08
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242835
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Legionella pneumophila</italic> (<italic>L</italic><italic>. pneumophila</italic>) is an intracellular bacterium of human alveolar macrophages that causes Legionnaires' disease. In contrast to humans, most inbred mouse strains are restrictive to <italic>L</italic>. <italic>pneumophila</italic> replication. We demonstrate that autophagy targets <italic>L</italic>. <italic>pneumophila</italic> vacuoles to lysosomes and that this process requires ubiquitination of <italic>L</italic>. <italic>pneumophila</italic> vacuoles and the subsequent binding of the autophagic adaptor p62/SQSTM1 to ubiquitinated vacuoles. The <italic>L</italic>. <italic>pneumophila leg</italic><italic>A</italic><italic>9</italic> encodes for an ankyrin‐containing protein with unknown role. We show that the <italic>leg</italic><italic>A</italic><italic>9</italic> mutant replicate in WT mice and their bone marrow‐derived macrophages. This is the first <italic>L</italic>. <italic>pneumophila</italic> mutant to be found to replicate in WT bone marrow‐derived macrophages other than the Fla mutant. Less <italic>leg</italic><italic>A</italic><italic>9</italic> 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 <italic>L</italic>. <italic>pneumophila</italic>‐containing vacuole for autophagy uptake.</p> </abstract>