Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis.
Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis.
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DOI：
10.1084/jem.20050125
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发表时间：
2005-05-16
影响因子：
15.3
通讯作者：
Moreillon, P
中科院分区：
文献类型：
--
作者：
Que, YA;Haefliger, JA;Piroth, L;François, P;Widmer, E;Entenza, JM;Sinha, B;Herrmann, M;Francioli, P;Vaudaux, P;Moreillon, P
金黄色葡萄球菌粘附素在乳酸乳球菌中的表达确定了凝集因子A（ClfA）和纤连蛋白结合蛋白A（FnBPA）是实验性心内膜炎大鼠瓣膜定植的关键。本研究进一步分析了它们在疾病演变中的作用。对感染动物进行3 d随访。ClfA阳性乳球菌成功地定殖受损的瓣膜，但在48小时内被自发根除。相反，FnBPA阳性乳球菌逐渐增加赘生物和脾脏中的细菌滴度。在成像中，ClfA阳性乳球菌仅限于赘生物，而FnBPA阳性乳球菌也侵入相邻的内皮。这反映了FnBPA在体外触发细胞内化的能力。由于FnBPA携带纤维蛋白原和纤连蛋白结合域，我们测试了这些功能的作用，删除FnBPA的纤维蛋白原结合域，并补充它与ClfA的纤维蛋白原结合域的顺式或反式。删除FnBPA的纤维蛋白原结合域并没有改变纤连蛋白结合和细胞内化在体外。然而，它完全消除了体内瓣膜感染性。通过将ClfA的纤维蛋白原结合结构域插入到截短的FnBPA中，顺式恢复这种能力，并且通过在两个单独的质粒上共表达全长ClfA和截短的FnBPA，反式恢复这种能力。因此，纤维蛋白原和纤连蛋白结合可协同作用于S。金黄色葡萄球菌瓣膜定殖和内皮侵入。
The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.
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影响因子：
3.6
作者：
GREENE, C;MCDEVITT, D;FOSTER, TJ
通讯作者：
FOSTER, TJ
影响因子：
3.6
作者：
MCDEVITT, D;FRANCOIS, P;FOSTER, TJ
通讯作者：
FOSTER, TJ
影响因子：
3.1
作者：
MOREILLON, P;ENTENZA, JM;VAUDAUX, P
通讯作者：
VAUDAUX, P
影响因子：
3.1
作者：
DANKERT, J;VANDERWERFF, J;HESS, J
通讯作者：
HESS, J
影响因子：
3.1
作者：
Bayles, KW;Wesson, CA;Trumble, WR
通讯作者：
Trumble, WR