Staphylococcal Proteases Aid in Evasion of the Human Complement System
Staphylococcal Proteases Aid in Evasion of the Human Complement System
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DOI：
10.1159/000351458
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发表时间：
2014-01-01
影响因子：
5.3
通讯作者：
Blom, Anna M.
中科院分区：
文献类型：
--
作者：
Jusko, Monika;Potempa, Jan;Blom, Anna M.
金黄色葡萄球菌是一种机会致病菌，由于多种耐药菌株的流行，引起了严重的卫生保健问题。迫切需要新的治疗策略，这需要了解疾病的致病机制。补体是抵抗细菌病原体的第一道防线之一，而S。金黄色葡萄球菌表达几种特异性补体抑制剂。然而，这种细菌的细胞外蛋白酶对补体的影响一直是有限研究的主题，除了最近的报道关于金霉素（Aur）裂解C3组分。我们在这里证明，四个主要的胞外蛋白酶的S。金黄色葡萄球菌是有效的补体抑制剂。半胱氨酸蛋白酶葡萄球菌蛋白酶A和葡萄球菌蛋白酶B，丝氨酸蛋白酶V8和金属蛋白酶Aur孵育的人血清导致血清的溶血活性急剧下降，而两种葡萄球菌丝氨酸蛋白酶D和E没有影响。发现这四种蛋白酶由于几种关键组分的有效降解而抑制补体的所有途径。此外，S.发现缺乏蛋白水解酶的金黄色葡萄球菌突变体在人血液中被更有效地杀死。综上所述，S.金黄色葡萄球菌似乎对于病原体介导的人补体系统逃避是重要的。(C)2013 S. Karger AG，巴塞尔
Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component by aureolysin (Aur). We demonstrate here that four major extracellular proteases of S. aureus are potent complement inhibitors. Incubation of human serum with the cysteine proteases staphopain A and staphopain B, the serine protease V8 and the metalloproteinase Aur resulted in a drastic decrease in the hemolytic activity of serum, whereas two staphylococcal serine proteases D and E, had no effect. These four proteases were found to inhibit all pathways of complement due to the efficient degradation of several crucial components. Furthermore, S. aureus mutants lacking proteolytic enzymes were found to be more efficiently killed in human blood. Taken together, the major proteases of S. aureus appear to be important for pathogen-mediated evasion of the human complement system. (C) 2013 S. Karger AG, Basel