Streptococcus iniae virulence is associated with a distinct genetic profile
Streptococcus iniae virulence is associated with a distinct genetic profile
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DOI：
10.1128/iai.69.4.1994-2000.2001
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发表时间：
2001-04-01
影响因子：
3.1
通讯作者：
de Azavedo, JCS
中科院分区：
文献类型：
--
作者：
Fuller, JD;Bast, DJ;de Azavedo, JCS
新链球菌可导致商业鱼类的脑膜脑炎和死亡，最近被确认为一种新的人类病原体，可引起暴发性软组织感染。通过脉冲场凝胶电泳(PFGE)鉴定，无论是在鱼还是在人类身上致病的菌株都属于单一克隆，而来自未患病鱼类的分离株在遗传上是多样化的。在这项研究中，我们使用体内和体外模型来检测与疾病相关的分离物的致病性。在皮下感染的小鼠模型中，具有克隆性(疾病相关)PFGE特征的菌株被发现可导致显著的体重减轻和菌血症。只要10(2)cfu的疾病相关菌株就足以建立菌血症，较高的接种量(10(7))会导致更高的死亡率。相反，非疾病相关(共生)菌株即使在接种10(8)CFU时也不能引起菌血症和体重减轻。此外，与几乎完全根除的共生菌株相比，疾病相关菌株在人类全血杀伤试验中对吞噬细胞清除的抵抗力更强。通过从宿主细胞释放乳酸脱氢酶来衡量，疾病相关菌株对人内皮细胞也具有细胞毒性。然而，疾病相关菌株和共生菌株对培养的人上皮细胞和内皮细胞的粘附性和侵袭性都一样好。虽然细胞入侵仍然可能是侵袭性新城疫的致病因素，但对吞噬清除的抵抗和直接的细胞毒性似乎是区分疾病相关克隆的毒力属性。
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.