中文摘要：由于口腔链球菌SF100菌株表达的噬菌体细胞裂解酶SM1能够介导细菌与纤维蛋白原的结合，是感染性心内膜炎发病机制的重要因素。为了更好地确定纤维蛋白原Aα上的细胞裂解酶（SM1）结合位点，并研究结合对纤维蛋白溶解的影响，本文研究了细胞裂解酶（SM1）与一系列重组纤维蛋白原Aα变体的相互作用。研究表明，细胞裂解酶（SM1）结合纤维蛋白原Aα跨越氨基酸残基534至610的C端区域，平衡解离常数（K-D）亲和力为3.23 x 10（-5）M。该结合位点与纤溶酶原已知结合位点重叠，纤溶酶原是纤溶酶的非活性前体，是降解纤维蛋白聚合物的关键蛋白酶。体外试验时，细胞裂解酶（SM1）竞争性抑制纤溶酶原与纤维蛋白原Aα的αC区结合。通过血栓弹性成像（TEG）测定，它还抑制纤溶酶原介导的纤维蛋白溶解作用，表明细胞裂解酶（SM1）是链球菌的一种双功能毒力因子，同时作为粘附素和纤溶酶原抑制剂。可见，细胞裂解酶（SM1）可能促进细菌附着在受损心脏瓣膜表面的纤维蛋白原上，也可能抑制纤溶酶原介导的瓣膜表面感染血栓（赘生物）的溶解。
    重点：在感染性心内膜炎的发病机制中，链球菌与人纤维蛋白原和血小板在受损的心内膜上的相互作用是一个主要因素。口腔链球菌可通过噬菌体细胞裂解酶（SM1）与血小板表面纤维蛋白原的相互作用与血小板结合，这一过程与心内膜炎动物模型的毒力增加有关。本文报道了细胞裂解酶（SM1）与人纤维蛋白原Aα链的αC区域结合，阻断了纤溶酶原与纤维蛋白原的结合并抑制纤维蛋白溶解。在体内，这种抑制作用可以防止受感染赘生物的分解，从而提高细菌的耐药性和毒力。
外文摘要：Expression of bacteriophage lysinSM1 by Streptococcus oralis strain SF100 is thought to be important for the pathogenesis of infective endocarditis, due to its ability to mediate bacterial binding to fibrinogen. To better define the lysin(SM1) bind-ing site on fibrinogen A alpha, and to investigate the impact of binding on fibrinolysis, we examined the interaction of lysin(SM1) with a series of recombinant fibrinogen A alpha variants. These studies revealed that lysin(SM1) binds the C-terminal region of fibrino-gen A alpha spanned by amino acid residues 534 to 610, with an affinity of equilibrium dissociation constant (K-D) of 3.23 x 10(-5) M. This binding site overlaps the known binding site for plasminogen, an inactive precursor of plasmin, which is a key prote-ase responsible for degrading fibrin polymers. When tested in vitro, lysin(SM1) competi-tively inhibited plasminogen binding to the alpha C region of fibrinogen A alpha. It also inhib-ited plasminogen-mediated fibrinolysis, as measured by thromboelastography (TEG). These results indicate that lysin(SM1) is a bi-functional virulence factor for streptococci, serving as both an adhesin and a plasminogen inhibitor. Thus, lysin(SM1) may facilitate the attachment of bacteria to fibrinogen on the surface of damaged cardiac valves and may also inhibit plasminogen-mediated lysis of infected thrombi (vegetations) on valve surfaces.
   IMPORTANCE The interaction of streptococci with human fibrinogen and platelets on damaged endocardium is a central event in the pathogenesis of infective endocardi-tis. Streptococcus oralis can bind platelets via the interaction of bacteriophage lysin(SM1) with fibrinogen on the platelet surface, and this process has been associated with increased virulence in an animal model of endocarditis. We now report that lysin(SM1) binds to the alpha C region of the human fibrinogen A alpha chain. This interaction blocks plasminogen binding to fibrinogen and inhibits fibrinolysis. In vivo, this inhibi-tion could prevent the lysis of infected vegetations, thereby promoting bacterial per-sistence and virulence.
外文关键词：Streptococcus mitis；fibrinogen；fibrinolysis；infective endocarditis；plasminogen；thromboelastography
作者：Ji, HJ；Zhi, Y；Lee, JH；Ahn, KB；Seo, HS；Sullam, PM
作者单位：Korea Atom Energy Res Inst；Univ Sci & Technol；Seoul Natl Univ；Univ Calif San Francisco；Vet Affairs Med Ctr
期刊名称：MBIO
期刊影响因子：4.778
出版年份：2021
出版刊次：3
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