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Streptococcus dysgalactiae, the long recognized mammalian pathogen, has currently received a major concern regarding fish bacterial infection. S. dysgalactiae caused either an opportunistic infection in immunocompromised patients or invasive infection in individuals handling livestock and seafood. The infected fish revealed systemic pyrogranulomatous inflammation with a severe necrotic lesion in their caudal peduncles. Despite increased clinical significance, the characterization of S. dysgalactiae strains isolated from different fish species collected in many countries and the epidemiological relationships among them have not been studied. Thus, little information is available concerning the outbreaks and epidemiology of S. dysgalactiae infection in farmed fish. Moreover, the origin, infection mechanism and the genetic basis of its virulence that characterize S. dysgalactiae as a fish pathogen remain unknown. Furthermore, no information is available on the initial step of fish-pathogen interaction. Therefore, the quest for a patent vaccine against this pathogen is hindered by the lack of knowledge regarding the pathogenesis and virulence determinants of S. dysgalactiae.