Document Detail


A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy.
MedLine Citation:
PMID:  23420491     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Arwa A Khweek; Kyle Caution; Anwari Akhter; Basant A Abdulrahman; Mia Tazi; Hoda Hassan; Neal Majumdar; Andrew Doran; Evelyn Guirado; Larry S Schlesinger; Howard Shuman; Amal O Amer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-08
Journal Detail:
Title:  European journal of immunology     Volume:  43     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2013-06-17     Revised Date:  2014-04-10    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1333-44     Citation Subset:  IM    
Copyright Information:
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics,  immunology
Animals
Autophagy / immunology*
Bacterial Proteins / genetics*,  immunology
Cells, Cultured
Heat-Shock Proteins / genetics,  immunology
Host Specificity
Host-Pathogen Interactions
Humans
Immune Evasion / genetics
Legionella pneumophila / genetics*,  immunology
Lysosomes / immunology,  metabolism,  microbiology
Macrophages / immunology,  microbiology*
Mice
Mutation*
Phagosomes / immunology,  metabolism,  microbiology
Protein Binding
Ubiquitin / metabolism
Ubiquitination
Vacuoles / immunology*,  metabolism,  microbiology
Grant Support
ID/Acronym/Agency:
R01 HL094586/HL/NHLBI NIH HHS; R01HL094586/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Bacterial Proteins; 0/Heat-Shock Proteins; 0/SQSTM1 protein, human; 0/Sqstm1 protein, mouse; 0/Ubiquitin
Comments/Corrections

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