The favorite host cell for M. tuberculosis is the macrophage. This pathogen not only survives in this cell, but adapted to transform this immune cell into an environment for its own replication. To study this process in more detail we use Mycobacterium marinum, the causative agent of fish tuberculosis, as model organism. We especially study the effect of T7S protein substrates on intracellular replication and the induction of host cell death. We have participated in research showing that ESX-1 is required for phagosomal escape in the macrophage. On the other hand, substrates of ESX-5 manipulate the host cell response and play an important role in macrophage cell death. In addition, using TraDIS analysis, we determined, on a genome wide level, the requirements of M. marinum for survival and replication in phagocytic cells from different origins. These experiments showed that M. marinum contains different sets of virulence factors that are tailored for phagocytic cells of different hosts. We are now exploring specific virulence factors in more detail. Another important aspect that we are studying is the relation between mycobacterial lipid body formation and bacterial persistence.