Oral Presentation 23rd Annual Lorne Proteomics Symposium 2018

Global mapping of Salmonella-host protein-protein interactions (#69)

Joel Selkrig 1 , Philipp Walch 1 , Keith Fernandez 1 , Mandy Rettel 1 , Frank Stein 1 , Mikhail Savitski 1 , Athanasios Typas 1
  1. EMBL, Heidelberg, Germany

To ensure survival and proliferation inside a host, bacterial pathogens inject a cocktail of toxic effector proteins directly into the host cell cytosol. Once injected, these effectors modify a broad range of host target proteins to facilitate pathogen survival. The intracellular pathogen Salmonella Typhimurium (STm) injects ~30 different effector proteins into host cells, however, knowledge of their targets is sparse. To systematically resolve the molecular interface between STm and the mammalian host during active infection, we infected macrophages with a library of STm strains expressing affinity tagged effector proteins from the endogenous chromosomal locus, followed by large scale Affinity-Purification and quantitative Mass-Spectrometry. In addition to validating several previously described protein-protein interactions, we uncovered a plethora of novel effector-host protein-protein interactions and, surprisingly, several novel effector-effector interactions. These findings provide the first molecular details of a complex host-pathogen interaction during active infection and have broad implications for the molecular basis of functional redundancies commonly observed for bacterial effector proteins.