Diseases caused by members of the family Vibrionaceae remain a significant cause of mortality and morbidity for marine animals worldwide, and some species are also of special concern for humans. We investigate how the marine bacterium Photobacterium damselae subsp. damselae has acquired the ability to cause infections in a wide range of marine animals and also in humans. An important pathogen in turbot aquaculture during the decade of 1990, P. damselae subsp. damselae constitutes nowadays an emerging pathogen in cultures of rainbow trout, sparid fish species and seabass. Its area of influence in Europe ranges from the Mediterranean coast to Denmark, and it is being increasingly isolated as causative agent of fish mortalities in the North African coast and in the Turkish coast of the Black Sea. All these data suggest that this pathogen is undergoing a fast adaptation to new fish species and to different conditions of water temperature and salinity. Regarding horizontal gene transfer, the acquisition of the virulence plasmid pPHDD1 that encodes the phospholipase-D damselysin (Dly) and the pore-forming toxin HlyApl, is at the basis of the emergence of a highly-virulent P. damselae subsp. damselae lineage that mostly affects turbot cultures. Interestingly, isolates lacking this plasmid are also virulent for fish and toxic for fish cell lines, and represent a high percentage of the isolates that caused recent outbreaks in fish aquaculture. Using genome sequencing of plasmidless strains and transposon-based mutagenesis, we are currently deciphering additional virulence factors that allow P. damselae subsp. damselae to cause disease in fish. Regulation of virulence gene expression by changes in the environmental conditions is also a topic of extreme interest. We study how variations in salinity and temperature affect virulence gene regulation in this pathogen. It is suspected that the increase in water temperature elicits P. damselae subsp. damselae outbreaks to occur, but to date there is no information about how temperature modulates virulence and fitness in this pathogen. We are exploring which genes allow P. damselae subsp. damselae to survive at 37ºC, an essential trait to replicate and invade human hosts. In addition, the decipheration of the roles of specific regulators as ToxR, H-NS proteins and two-component regulatory systems, and the analysis of post-translational maturation of the HlyA pore-forming toxin, constitute current topics of our investigation. The duality of P. damselae subsp. damselae as a pathogen for both poikilotherm and homeotherm animals makes this bacterium a valuable biological model to study the genome adaptations that lead to the rise of novel pathogenic strategies.