Bacterial infections represent a rising threat on human health. They result from complex molecular interactions between a large number of microbial components and host factors, and therefore, need to be addressed on a global scale. Using the enteroinvasive bacterium Shigella flexneri as main model of infection, we combine systems biology methods and mechanistic approaches to characterize the host molecular pathways involved in several key aspects of bacterial infections including invasion of epithelial cells, host cell survival and inflammation.
The emergence of multi-drug-resistance mechanisms among major pathogenic bacteria represents a rising threat on human health. The lack of new therapeutic options requires an urgent effort of the scientific community to identify new microbial targets and envision alternative strategies. A promising approach consists of targeting the host instead of the pathogen. Indeed, it became clear over the last years, that pathogens subvert key cellular factors and responses in order to infect their host. Blocking the expressing of these factors or interfering with their activities may prevent colonization and have a positive impact on the infection outcome. Since infections result from countless molecular interactions between microbial components and host factors, identifying key cellular targets requires mapping these interactions on a global scale.
Using the enteroinvasive bacterium Shigella flexneri as main model, we apply systems biology methods including large scale RNAi screens and phosphoproteomics to identify and characterize the cellular pathways that are required for bacterial invasion of epithelial cells, survival of infected cells and inflammation, three central aspects of S. flexneri pathogenesis.
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