Streptococcus iniae virulence is associated with a distinct genetic profile

Streptococcus iniae causes meningoencephalitis and death in commercial fish species and has recently been identified as an emerging human pathogen pro ducing fulminant soft tissue infection. As identified by pulsed-field gel e lectrophoresis (PFGE), strains causing disease in either fish or humans bel ong to a single clone, whereas isolates from nondiseased fish are genetical ly diverse. In this study, we used in vivo and in vitro models to examine t he pathogenicity of disease-associated isolates. Strains with the clonal (d isease-associated) PFGE profile were found to cause significant weight loss and bacteremia in a mouse model of subcutaneous infection. As little as 10 (2) CFU of a disease associated strain was sufficient to establish bacterem ia, with higher inocula (10(7)) resulting in increased mortality. In contra st, non-disease-associated (commensal) strains failed to cause bacteremia a nd weight loss, even at inocula of 10(8) CFU. In addition, disease associat ed strains were more resistant to phagocytic clearance in a human whole blo od killing assay compared to commensal strains, which were almost entirely eradicated. Disease-associated strains were also cytotoxic to human endothe lial cells as measured by lactate dehydrogenase release from host cells. Ho wever, both disease associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well. While cellul ar invasion may still contribute to the pathogenesis of invasive S. iniae d isease, resistance to phagocytic clearance and direct cytotoxicity appear t o be discriminating virulence attributes of the disease-associated clone.