Photobacterium damselae subsp. damselae is an emerging pathogen of marine aquaculture. By combining phenotypic and genotypic data, and comparative genomics analyses, we here show that this pathogen exhibits a high genetic diversity and that outbreaks in fish are caused by multiclonal populations. We identified and characterized the RstAB two-component signal transduction system, a major positive regulator of virulence and of many aspects of cell physiology in this bacterium. The RstAB regulon comprises the major cytotoxins Dly, PhlyP and PhlyC, as well as hitherto unreported proteins secreted by the type two secretion system (T2SS), that may constitute novel virulence factors in this pathogen.
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