Interactions Métaboliques Hôte-Pathogène: Comment des Bactéries Intracellulaires détournent l’OXPHOS Mitochondriale pendant l’infection
Infectious diseases are a major threat to human health and predictions suggest that over the next few decades, these will account for one of five deaths globally. In times where emergence of antibiotic-resistance in bacteria is occurring worldwide, understanding how bacteria cause disease is essential to finding new therapeutic approaches to tackle infection. We have recently shown that the intracellular bacterium Legionella pneumophila, which causes Legionaries’ disease in humans, alters mitochondrial oxidative phosphorylation (OXPHOS) and ATP production during infection of human macrophages. This project now aims to understand the mechanism(s) by which L. pneumophila hijack the mitochondrial OXPHOS machinery. By combining state-of-the-art image-based methods with bacterial genetics, si-RNA silencing, proteomics, and cellular biology approaches, we expect to identify new mechanisms pathogenic bacteria employ to subvert mitochondrial functions in infected human macrophages.
Figure: hMDMs infected with L. pneumophila strain Paris WT-GFP (green) and labeled with Hoechst (pale blue) to identify cell nucleus and TMRM (red) to quantify mΔΨ. Time post-infection (hours) is indicated. Bar: 20 μm