Quantitative analysis of host immune response against bacterial infection
Evgenij Fiskin, Tihana Bionda, Sjoerd van Wijk, Christian Behrends and Ivan Đikić. Institute of Biochemistry II, Goethe University School of Medicine and Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt
Post-translational modification by ubiquitin (Ub) plays an important role in various aspects of cellular life. Recently it emerged as a signal that marks cargo for lysosomal degradation via selective autophagy. Selective anti-bacterial autophagy is initiated upon damage to bacteria-containing vacuoles and exposure of bacteria to the host cytosol where they rapidly associate with poly-ubiquitin.
We and others have shown that the dense ubiquitin coat surrounding cytosolic Salmonella typhimurium recruits autophagy receptors and leads to subsequent loading of bacteria into autophagosomes.
Although the involvement of bacterially localized ubiquitin as a recruitment platform for autophagy receptors is characterized, the modified substrates as well as assembly dynamics of this ubiquitin coat have not been addressed so far. Using stable isotope labeling by amino acids in cell culture (SILAC) combined with LC-MS analysis, we identified differentially ubiquitinated proteins during Salmonella infection.
We are currently elucidating the role of differential ubiquitination of candidate proteins and will present our progress in this area.
