title: The DUB-ious lack of ALIS in Salmonella infection: a Salmonella deubiquitinase regulates the autophagy of protein aggregates.
abstract: Ubiquitinated aggregates are formed in eukaryotic cells in response to several external stimuli, including exposure to bacterial lipopolysaccharide (LPS). Although Salmonella enterica serovar Typhimurium (S. Typhimurium) LPS has been shown to induce aggresome-like induced structures (ALIS) in macrophages, these have not been described in S. Typhimurium-infected macrophages. Given that LPS is present in infection, this suggests that S. Typhimurium might suppress the formation of ALIS. We found that S. Typhimurium induces the formation of ubiquitinated aggregates in epithelial cells and macrophages, but that their presence is masked by the deubiquitinase (DUB) activity of the S. Typhimurium virulence protein, SseL. SseL deubiquitinates SQSTM1/p62-bound proteins found in S. Typhimurium-induced aggregates and ALIS, and reduces the recruitment of autophagic components. While the functions of ALIS and other ubiquitinated aggregates remain unclear, they serve to sequester cytosolic proteins under a variety of stress conditions and are suggested to be involved in host immune defense. During infection, the deubiquitinase activity of SseL reduces autophagic flux in infected cells and favors bacterial replication. This is a new example of how a bacterial pathogen counteracts the autophagy pathway through the action of a translocated virulence protein.
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK. mair.thomas@imperial.ac.uk
authors.forename: Mair
authors.initials: M
authors.lastname: Thomas
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Mesquita
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D000818:Animals; D001343:Autophagy; D003600:Cytosol / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D008954:Models, Biological; D020836:Protein Structure, Quaternary; D012475:Salmonella / Q000201:enzymology*; D012480:Salmonella Infections / Q000473:pathology*; D054875:Ubiquitination
chemical_list: D010450:Endopeptidases