Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains.
Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains.
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DOI：
10.1074/jbc.ra117.000599
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发表时间：
2018-03-23
期刊：
影响因子：
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通讯作者：
Rooijakkers SHM
中科院分区：
文献类型：
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作者：
de Jong NWM;Vrieling M;Garcia BL;Koop G;Brettmann M;Aerts PC;Ruyken M;van Strijp JAG;Holmes M;Harrison EM;Geisbrecht BV;Rooijakkers SHM
金黄色葡萄球菌是一种多功能病原体，能够在许多不同的宿主中引起广泛的疾病。S.金黄色葡萄球菌可以通过其基因组的修饰（例如通过获得和交换编码宿主特异性毒力因子的移动的遗传元件）来适应其宿主。最近在S.金黄色葡萄球菌菌株来自六个不同的克隆谱系，几乎完全分离自马科动物。在这种噬菌体中，我们发现了一种新的葡萄球菌补体抑制剂（SCIN）变体，SCIN是一种分泌蛋白，可干扰人体补体系统的激活，这是宿主防御的重要防线。我们在这里表明，这种马的变异SCIN，eqSCIN，是一种有效的阻断剂马补体系统激活和随后的吞噬细胞吞噬细菌。机制研究表明，eqSCIN通过特异性抑制C3转化酶（C3 bBb）阻断马补体激活。而人S.由于金黄色葡萄球菌分离株仅抑制人补体，eqSCIN代表了第一个在更广泛宿主（马、人和猪）中发挥作用的动物适应性SCIN变体。结合分析表明，SCIN-A的人类特异性活性与SCIN-C3 b界面两侧的氨基酸差异有关。这些数据表明，这种噬菌体编码的补体抑制剂的修饰在S.金黄色葡萄球菌和重要的是了解这种病原体如何在不同的主机之间转移。
Staphylococcus aureus is a versatile pathogen capable of causing a broad range of diseases in many different hosts. S. aureus can adapt to its host through modification of its genome (e.g. by acquisition and exchange of mobile genetic elements that encode host-specific virulence factors). Recently, the prophage φSaeq1 was discovered in S. aureus strains from six different clonal lineages almost exclusively isolated from equids. Within this phage, we discovered a novel variant of staphylococcal complement inhibitor (SCIN), a secreted protein that interferes with activation of the human complement system, an important line of host defense. We here show that this equine variant of SCIN, eqSCIN, is a potent blocker of equine complement system activation and subsequent phagocytosis of bacteria by phagocytes. Mechanistic studies indicate that eqSCIN blocks equine complement activation by specific inhibition of the C3 convertase enzyme (C3bBb). Whereas SCIN-A from human S. aureus isolates exclusively inhibits human complement, eqSCIN represents the first animal-adapted SCIN variant that functions in a broader range of hosts (horses, humans, and pigs). Binding analyses suggest that the human-specific activity of SCIN-A is related to amino acid differences on both sides of the SCIN-C3b interface. These data suggest that modification of this phage-encoded complement inhibitor plays a role in the host adaptation of S. aureus and are important to understand how this pathogen transfers between different hosts.