Projekt

Collaborative Research Consortium CDInfect - Adaptation strategies of Clostridioides difficile during host infection: Structure and function of protein interaction networks required for infection with C. difficile

Living organisms require protein interaction networks to react to environmental cues. This enables them to colonize different habitats including host organisms, where they may become virulent in the case of microbial pathogens. Clostridium difficile colonizes the intestine of infected patients, where it damages host tissue through the action toxins TcdA and TcdB. While the activities of TcdA/B are well understood, nothing is known about protein interaction networks required for their generation. Toxin production is linked to the availability of amino acids that C. difficile uses for energy conservation, e.g. in a process known as “Stickland fermentation”. This pathway involves large protein complexes to reduce amino acids and to utilize the gained metabolic energy for ATP generation. We investigate these complexes by using an integrative approach that dwells on cross-linking mass spectrometry and structural biology. Our spectrum of methods is further expanded through close collaborations with other groups of the consortium to cover e.g. C. difficile fermentation or metabolomic analysis.

Long term goals of this project are to derive a detailed molecular understanding of the interplay between toxin production and amino acid metabolism in C. difficile, as well as unravelling new and unique protein interaction networks that the pathogen requires to cause infectious disease. Ultimately, this insight may unravel opportunities for the development of new pharmaceuticals against C. difficile.