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首页> 外文期刊>Infection and immunity >Cleavage of Antigen-Bound Immunoglobulin G by SpeB Contributes to Streptococcal Persistence in Opsonizing Blood
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Cleavage of Antigen-Bound Immunoglobulin G by SpeB Contributes to Streptococcal Persistence in Opsonizing Blood

机译：SpeB对抗原结合的免疫球蛋白G的裂解有助于调理血液中链球菌的持久性

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Group A streptococci (GAS) express a superantigen, SpeB, having cysteine protease activity. SpeB exhibits several properties that might contribute to virulence, the most recently discovered being the ability to cleave immunoglobulin G (IgG) in a manner similar to that of papain. In the present study, we confirmed this latter finding and found that the irreversible inhibition of SpeB protease activity completely abolishes IgG cleavage. SpeB cleavage of IgG was not species restricted since SpeB cleaved both human, rabbit, and mouse IgG. In order to investigate the nature of the SpeB cleavage of IgG, antibodies were immobilized prior to exposure to SpeB, either by unspecific binding of the Fc to GAS surface proteins or by antigen-specific binding. Analysis of the IgG molecules by SDS-PAGE showed that SpeB could cleave antigen-bound antibodies, while the IgG bound to IgG-binding proteins was protected from cleavage. In a phagocytosis assay using whole blood, the M49 GAS strain NZ131 showed a significantly higher survival than its isogenic speB mutant. Furthermore, the addition of extracellular supernatant derived from an overnight culture of native NZ131 increased the survival of its isogenic speB derivative. This indicates that SpeB's ability to cleave off the Fc part of antigen-bound IgG contributes to GAS escape from opsonophagocytosis while not interfering with the formation of a host-like coat by unspecific IgG binding.
机译：A组链球菌（GAS）表达具有半胱氨酸蛋白酶活性的超抗原SpeB。 SpeB表现出几种可能会导致毒性的特性，最近发现的特性是能够以类似于木瓜蛋白酶的方式裂解免疫球蛋白G（IgG）。在本研究中，我们证实了后者的发现，并发现SpeB蛋白酶活性的不可逆抑制作用完全消除了IgG裂解。 IgG的SpeB裂解不受物种限制，因为SpeB裂解了人，兔和小鼠IgG。为了研究IgG的SpeB裂解的性质，在暴露于SpeB之前，通过Fc与GAS表面蛋白的非特异性结合或通过抗原特异性结合来固定抗体。通过SDS-PAGE分析IgG分子显示，SpeB可以裂解抗原结合的抗体，而与IgG结合蛋白结合的IgG被保护免于裂解。在使用全血的吞噬作用分析中，M49 GAS菌株NZ131显示出比同基因的 speB 突变体更高的存活率。此外，添加来自天然NZ131过夜培养物的细胞外上清液可提高其同基因 speB 衍生物的存活率。这表明SpeB切割掉抗原结合的IgG的Fc部分的能力有助于GAS从调理吞噬作用中逸出，同时不干扰非特异性IgG结合形成宿主样外壳。

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