Dictyostelium as a model phagocyte to study both cell-autonomous and altruistic defence against (myco)bacteria infection

The first line of defence against bacterial infections are phagocytic cells of the innate immune system. While multicellular organisms use phagocytosis to kill microbes and initiate a sustained immune response, phagocytic amoebae internalise bacteria as nutrients, via mechanisms of recognition, signalling and killing that are surprisingly conserved with innate immune phagocytes. Dictyostelium is a social amoeba that feeds by phagocytosis and has ancestral, highly conserved cell-autonomous defence systems. It is genetically and biochemically tractable and has emerged as a powerful and experimentally versatile model to study various bacterial pathogens. The causative agent of tuberculosis, Mycobacterium tuberculosis, infects alveolar macrophages and subverts their bactericidal pathways that normally protect the lungs from infection. Important aspects of mycobacteria pathogenicity and host defences during infection remain to be explored. We study the mechanisms of infection by Mycobacterium marinum, a close cousin of M. tuberculosis, which uses similar virulence strategies to re-program and proliferate inside macrophages. In particular, we use this Dictyostelium/M. marinum model to study the inter-relationships between host and pathogen in terms of nutritional immunity, acquisition of metabolites, interference with the membrane trafficking and cytsokeletal processes. Recently, we have strongly focused on the pathways responding and repairing bacteria-mediated membrane damages, manipulation of autophagy and acquisition of lipids from the host. We have also used this infection model to perform medium-throughput screens for anti-infective compounds with low antibiotic activity that revealed the possibility to develop compounds for host-directed anti-infectious strategies.