Staphylococcus aureus proteins Sbi and Efb recruit human plasmin to degrade complement C3 and C3b.

Staphylococcus aureus proteins Sbi and Efb recruit human plasmin to degrade complement C3 and C3b.
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DOI:
10.1371/journal.pone.0047638
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Skerka C
Skerka C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Koch TK;Reuter M;Barthel D;Böhm S;van den Elsen J;Kraiczy P;Zipfel PF;Skerka C

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当宿主感染人类病原微生物金黄色葡萄球菌(S. aureus)时,立即面临激活补体系统等先天免疫反应。本文描述了一种新的金黄色葡萄球菌先天免疫逃避策略。葡萄球菌蛋白表面免疫球蛋白结合蛋白(Sbi)和细胞外纤维蛋白原结合蛋白(Efb)与纤溶酶原同时结合C3/C3b。结合的纤溶酶原通过细菌激活剂葡萄激酶或宿主特异性尿激酶型纤溶酶原激活剂转化为纤溶酶,进而导致补体C3和C3b的降解。Efb和Sbi在较小程度上增强了C3/C3b的纤溶酶裂解,这种作用可以解释为Sbi和Efb诱导C3/C3b的构象变化。此外,结合的纤溶蛋白还能降解C3a,从而发挥过敏和抗菌活性。因此,金黄色葡萄球菌Sbi和Efb包括募集纤溶酶(原)的平台,以及C3及其激活产物C3b,以在局部微生物环境中有效降解这些补体成分,并保护金黄色葡萄球菌免受宿主先天免疫反应的影响。
Upon host infection, the human pathogenic microbe Staphylococcus aureus (S. aureus) immediately faces innate immune reactions such as the activated complement system. Here, a novel innate immune evasion strategy of S. aureus is described. The staphylococcal proteins surface immunoglobulin-binding protein (Sbi) and extracellular fibrinogen-binding protein (Efb) bind C3/C3b simultaneously with plasminogen. Bound plasminogen is converted by bacterial activator staphylokinase or by host-specific urokinase-type plasminogen activator to plasmin, which in turn leads to degradation of complement C3 and C3b. Efb and to a lesser extend Sbi enhance plasmin cleavage of C3/C3b, an effect which is explained by a conformational change in C3/C3b induced by Sbi and Efb. Furthermore, bound plasmin also degrades C3a, which exerts anaphylatoxic and antimicrobial activities. Thus, S. aureus Sbi and Efb comprise platforms to recruit plasmin(ogen) together with C3 and its activation product C3b for efficient degradation of these complement components in the local microbial environment and to protect S. aureus from host innate immune reactions.
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