A holistic approach to host- pathogen interactions

Sepsis is one of the leading causes of mortality and morbidity in the world, and is an overreaction by the immune system due to pathogen invasion of the bloodstream. The interactions, particularly the protein interactions, between the host and pathogen are fundamental for the outcome of the disease. However, some of the protein interactions are unknown and those that are known have been studied as single entities. This thesis focuses on expanding the knowledge of these interactions. In addition, the thesis emphasises the analysis of every interaction at the same time. The identification and quantification of the whole network of interactions is central to determine the impact of single proteins, since the interactions can be co-dependent. The proteins of the human immune system are of particular interest since the pathogens have to avoid the immune system in order to survive in the host. Using state of the art techniques, the human plasma interaction proteome for several pathogens were determined and several novel interactions were discovered. For the gram-positive bacterium Streptococcus pyogenes, the interaction proteome was determined with higher accuracy than ever before. In conclusion, when focusing on the whole interaction pattern the specific details can be explained. The wider understanding of the field of host-pathogen interactions that is established with this thesis aids in future development of diagnostics and therapeutics in pathogen related diseases.