Essential and virulence genes of M. marinum and M. tuberculosis are highly similar M. marinum has different sets of virulence factors customized for specific hosts The auxiliary proteins of ESX-1 play a crucial role in host specificity. Mycobacterium marinum E11

Mycobacterium marinum is an intracellular pathogen that can infect and replicate in vertebrates as well as in protozoan species. Using transposon-directed insertion-site sequencing (TraDIS), we investigated which virulence factors are required for different host cells and discovered a number of general virulence mechanisms relevant for all hosts, including type VII protein secretion, biosynthesis of the polyketide lipids and utilisation of sterols. Interestingly, our data also showed that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 type VII secretion system. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific host. Our data implies that amoeba could function as a training ground for intracellular pathogens, but they do not fully prepare pathogens for crossing species barriers.