A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen
A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen
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DOI：
10.1172/jci200316270
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发表时间：
2003-01-01
影响因子：
15.9
通讯作者：
Rubens, CE
中科院分区：
文献类型：
--
作者：
Harris, TO;Shelver, DW;Rubens, CE
B族链球菌（GBS）是人类重要的病原体。在这项研究中，我们试图确定机制，可能保护GBS从宿主防御除了其荚膜多糖。编码细胞表面相关蛋白（cspA）的基因，其特征在于从高毒力III型GBS分离株，COH 1。其序列表明，它是一种枯草杆菌蛋白酶样胞外丝氨酸蛋白酶，与链球菌C5 a肽酶和乳酸菌的酪蛋白酶同源。野生型菌株切割人纤维蛋白原的α链，而cspA突变体TOH 121不能切割纤维蛋白原。我们观察到聚集的材料时，COH 1与纤维蛋白原孵育，但不是当突变株进行类似的处理。这表明纤维蛋白原裂解产物具有强粘附性，可能与纤维蛋白相似。cspA基因存在于所有9种荚膜血清型的代表性临床分离株中，如Southern印迹所示。通过LD 50分析测量，cspA（-）突变体在GBS感染的新生大鼠脓毒症模型中的毒力降低10倍。此外，cspA突变体在体外对人嗜中性粒细胞的调理吞噬杀伤比野生型菌株显著更敏感。总之，结果表明，CspA对纤维蛋白原的切割可能会增加GBS感染的致死率，可能是通过保护细菌免受调理吞噬杀伤。
Group B streptococcus (GBS) is an important human pathogen. In this study, we sought to identify mechanisms that may protect GBS from host defenses in addition to its capsular polysaccharide. A gene encoding a cell-surface-associated protein (cspA) was characterized from a highly virulent type III GBS isolate, COH1. Its sequence indicated that it is a subtilisin-like extracellular serine protease homologous to streptococcal C5a peptidases and caseinases of lactic acid bacteria. The wild-type strain cleaved the a chain of human fibrinogen, whereas a cspA mutant, TOH121, was unable to cleave fibrinogen. We observed aggregated material when COH1 was incubated with fibrinogen but not when the mutant strain was treated similarly. This suggested that the product(s) of fibrinogen cleavage have strong adhesive properties and may be similar to fibrin. The cspA gene was present among representative clinical isolates from all nine capsular serotypes, as revealed by Southern blotting. A cspA(-) mutant was ten times less virulent in a neonatal rat sepsis model of GBS infections, as measured by LD50 analysis. In addition, the cspA- mutant was significantly more sensitive than the wildtype strain to opsonophagocytic killing by human neutrophils in vitro. Taken together, the results suggest that cleavage of fibrinogen by CspA may increase the lethality of GBS infection, potentially by protecting the bacterium from opsonophagocytic killing.