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 producing fulminant soft tissue infection. As identified by pulsed-field gel electrophoresis (PFGE), strains causing disease in either fish or humans belong to a single clone, whereas isolates from nondiseased fish are genetically diverse. In this study, we used in vivo and in vitro models to examine the pathogenicity of disease-associated isolates. Strains with the clonal (disease-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 bacteremia, with higher inocula (10(7)) resulting in increased mortality. In contrast, non-disease-associated (commensal) strains failed to cause bacteremia and weight loss, even at inocula of 10(8) CFU. In addition, disease-associated strains were more resistant to phagocytic clearance in a human whole blood killing assay compared to commensal strains, which were almost entirely eradicated. Disease-associated strains were also cytotoxic to human endothelial cells as measured by lactate dehydrogenase release from host cells. However, both disease-associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well. While cellular invasion may still contribute to the pathogenesis of invasive S. iniae disease, resistance to phagocytic clearance and direct cytotoxicity appear to be discriminating virulence attributes of the disease-associated clone.

海豚链球菌（Streptococcus iniae）可引发经济鱼类的脑膜脑炎并导致死亡，近年来还被鉴定为一种新兴人类致病菌，可引起暴发性软组织感染。经脉冲场凝胶电泳（PFGE）分析发现，引发鱼类或人类疾病的菌株均属于同一克隆型，而从无病变鱼类中分离得到的菌株则具有丰富的遗传多样性。本研究借助体内与体外模型，对致病相关分离株的致病性展开了系统性研究。带有该克隆型（致病相关）PFGE图谱的菌株，在小鼠皮下感染模型中可引发显著的体重减轻与菌血症；仅需10² CFU的致病相关菌株即可建立菌血症感染，更高接种量（10⁷ CFU）则会提升宿主死亡率。与之形成鲜明对比的是，非致病相关（共生）菌株即便以10⁸ CFU的接种量进行感染，也无法引发菌血症与体重减轻。此外，相较于几乎被完全清除的共生菌株，致病相关菌株在人类全血杀菌实验中表现出更强的吞噬清除抵抗能力。通过检测宿主细胞释放的乳酸脱氢酶水平可知，致病相关菌株对人类内皮细胞具有细胞毒性。不过，两类菌株对培养的人类上皮细胞与内皮细胞的黏附及侵袭能力并无显著差异。尽管细胞侵袭或许仍有助于侵袭性海豚链球菌病的发病进程，但抵抗吞噬清除与直接细胞毒性，似乎是该致病相关克隆株区别于其他菌株的核心毒力特征。