Final Report Summary - PATHOPROT (In vivo pathogen proteome profiling using selected reaction monitoring)
Bacterial infections represent a major global health problem, which is further aggravated by the rapid and ongoing increase in antibiotic resistance. The limited success in the development of targeted therapies for invasive strains can be attributed to the limited knowledge how pathogens modulate their proteome homeostasis in vivo, knowledge that has so far remained elusive due to technical limitations.
In this project we have used quantitative mass spectrometry-based proteomics for pathogen proteome profiling from in vivo samples using group A streptococci (GAS) as a model system. GAS is a common colonizer of the skin and the upper respiratory tract where it causes relatively mild clinical conditions such as impetigo and pharyngitis. GAS can also penetrate into deeper tissues and cause severe and potentially life-threatening conditions such as necrotizing fasciitis and sepsis. Over the course of the project we have constructed a comprehensive and quantitative molecular anatomy knowledge model outlining the spatial organization of a microbial proteome and its protein-protein interaction network with human host proteins. Using the molecular anatomy, we have investigated quantitative and structural changes in the host-pathogen relationship to determine critically important mechanisms for the development of invasive and severe infectious diseases.
The project has generated a generic strategy to provide increased understanding of pathogen adaption in vivo. This project has due to the high level of interdisciplinary components, enlightened central aspects within the medical microbiology field. The most important technologies and findings derived from this project may be of particular relevance for the development of new vaccines and targeted treatments, which is of critical importance considering the increasing number antibiotic resistance strains in Europe and the rest of the world.
In this project we have used quantitative mass spectrometry-based proteomics for pathogen proteome profiling from in vivo samples using group A streptococci (GAS) as a model system. GAS is a common colonizer of the skin and the upper respiratory tract where it causes relatively mild clinical conditions such as impetigo and pharyngitis. GAS can also penetrate into deeper tissues and cause severe and potentially life-threatening conditions such as necrotizing fasciitis and sepsis. Over the course of the project we have constructed a comprehensive and quantitative molecular anatomy knowledge model outlining the spatial organization of a microbial proteome and its protein-protein interaction network with human host proteins. Using the molecular anatomy, we have investigated quantitative and structural changes in the host-pathogen relationship to determine critically important mechanisms for the development of invasive and severe infectious diseases.
The project has generated a generic strategy to provide increased understanding of pathogen adaption in vivo. This project has due to the high level of interdisciplinary components, enlightened central aspects within the medical microbiology field. The most important technologies and findings derived from this project may be of particular relevance for the development of new vaccines and targeted treatments, which is of critical importance considering the increasing number antibiotic resistance strains in Europe and the rest of the world.