Document Detail


The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates.
MedLine Citation:
PMID:  22719249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell stress and infection promote the formation of ubiquitinated aggregates in both non-immune and immune cells. These structures are recognised by the autophagy receptor p62/sequestosome 1 and are substrates for selective autophagy. The intracellular growth of Salmonella enterica occurs in a membranous compartment, the Salmonella-containing vacuole (SCV), and is dependent on effectors translocated to the host cytoplasm by the Salmonella pathogenicity island-2 (SPI-2) encoded type III secretion system (T3SS). Here, we show that bacterial replication is accompanied by the formation of ubiquitinated structures in infected cells. Analysis of bacterial strains carrying mutations in genes encoding SPI-2 T3SS effectors revealed that in epithelial cells, formation of these ubiquitinated structures is dependent on SPI-2 T3SS effector translocation, but is counteracted by the SPI-2 T3SS deubiquitinase SseL. In macrophages, both SPI-2 T3SS-dependent aggregates and aggresome-like induced structures (ALIS) are deubiquitinated by SseL. In the absence of SseL activity, ubiquitinated structures are recognized by the autophagy receptor p62, which recruits LC3 and targets them for autophagic degradation. We found that SseL activity lowers autophagic flux and favours intracellular Salmonella replication. Our data therefore show that there is a host selective autophagy response to intracellular Salmonella infection, which is counteracted by the deubiquitinase SseL.
Authors:
Francisco S Mesquita; Mair Thomas; Martin Sachse; António J M Santos; Rita Figueira; David W Holden
Related Documents :
1468599 - Immune-neuroendocrine circuits: integrative role of cytokines.
22319619 - Persistence versus escape: aspergillus terreus and aspergillus fumigatus employ differe...
22912809 - Arachidonate 15-lipoxygenase type b knockdown leads to reduced lipid accumulation and i...
22861359 - Lymph node dissection--understanding the immunological function of lymph nodes.
22771209 - Ligation of fc gamma receptor iib enhances levels of antiviral cytokine in response to ...
22291719 - Cholinergic regulation of airway inflammation and remodelling.
21701599 - Fty720 reduces post-ischemic brain lymphocyte influx but does not improve outcome in pe...
8450029 - Local expression of antiinflammatory cytokines in cancer.
19483409 - new therapeutic strategy for autoimmune and chronic inflammatory disease based on clini...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-14
Journal Detail:
Title:  PLoS pathogens     Volume:  8     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-11-09     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1002743     Citation Subset:  IM    
Affiliation:
Section of Microbiology, Centre for Molecular Microbiology and Infection, Imperial College London, London, United Kingdom.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy*
Bacterial Proteins / metabolism*
Cell Line
Cytosol / metabolism,  parasitology
Endopeptidases / metabolism*
Epithelial Cells / parasitology*
Humans
Immunoblotting
Immunoprecipitation
Macrophages / parasitology
Mice
Microscopy, Confocal
Microscopy, Fluorescence
Microscopy, Immunoelectron
Salmonella Infections / metabolism*
Salmonella enterica / enzymology*
Ubiquitin / metabolism
Vacuoles / metabolism,  parasitology
Grant Support
ID/Acronym/Agency:
092686/Z/10/Z//Wellcome Trust; G0800148//Medical Research Council
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Ubiquitin; EC 3.4.-/Endopeptidases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced ris...
Next Document:  A high-resolution view of genome-wide pneumococcal transformation.