title: Global Analysis of Host and Bacterial Ubiquitinome in Response to Salmonella Typhimurium Infection.
abstract: Ubiquitination serves as a critical signal in the host immune response to infection. Many pathogens have evolved strategies to exploit the ubiquitin (Ub) system to promote their own survival through a complex interplay between host defense machinery and bacterial virulence factors. Here we report dynamic changes in the global ubiquitinome of host epithelial cells and invading pathogen in response to Salmonella Typhimurium infection. The most significant alterations in the host ubiquitinome concern components of the actin cytoskeleton, NF-κB and autophagy pathways, and the Ub and RHO GTPase systems. Specifically, infection-induced ubiquitination promotes CDC42 activity and linear ubiquitin chain formation, both being required for NF-κB activation. Conversely, the bacterial ubiquitinome exhibited extensive ubiquitination of various effectors and several outer membrane proteins. Moreover, we reveal that bacterial Ub-modifying enzymes modulate a unique subset of host targets, affecting different stages of Salmonella infection.
authors.affiliation: Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Evgenij
authors.initials: E
authors.lastname: Fiskin
authors.affiliation: Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Tihana
authors.initials: T
authors.lastname: Bionda
authors.affiliation: Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University, Max-von-Laue-Strasse 15, 60438 Frankfurt am Main, Germany; Department of Immunology and Medical Genetics, School of Medicine, University of Split, Soltanska 2, 21 000 Split, Croatia. Electronic address: ivan.dikic@biochem2.de.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
authors.affiliation: Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: behrends@biochem2.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Behrends
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D045325:HCT116 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000378:metabolism* / Q000472:pathogenicity; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016328:NF-kappa B; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase; D020764:cdc42 GTP-Binding Protein