Departments of Rheumatology and Inflammation Research, Sahlgrenska Academy, Gothenburg University, Box 480, 40530 Göteborg, Sweden.
J Infect Dis. 2010 Oct 1;202(7):1041-9. doi: 10.1086/656140.
Staphylokinase (SAK) is produced by the majority of Staphylococcus aureus strains. It is an extracellular protein that activates the conversion of human plasminogen (plg) to plasmin. The role played by SAK in staphylococcal infection is unclear.
Wild-type S. aureus strain LS-1, which lacks the ability to produce SAK, was modified by an insertion of the sak gene into its chromosome. The sak gene was integrated in 2 forms--(1) linked to its own promoter and (2) fused to the promoter of the protein A gene--which resulted in the overexpression of SAK. SAK is highly specific for human plg and exhibits almost no activity toward murine plg. To investigate the role played by SAK in a murine infection model, human plg transgenic mice and their wild-type counterparts were inoculated intravenously with congenic S. aureus strains differing in SAK production.
Human plg transgenic mice inoculated with SAK-expressing strains displayed significantly reduced mortality, less weight loss, and lower bacterial loads in kidneys than did the wild-type mice. No difference in the severity of sepsis was observed between transgenic and wild-type mice infected with a SAK-deficient strain.
The results suggest that expression of SAK followed by activation of plg alleviates the course of S. aureus sepsis.
金黄色葡萄球菌（SAK）是由大多数金黄色葡萄球菌株产生的。它是一种细胞外蛋白，可激活人纤溶酶原（plg）向纤溶酶的转化。SAK 在葡萄球菌感染中的作用尚不清楚。
野生型金黄色葡萄球菌 LS-1 缺乏产生 SAK 的能力，通过将 sak 基因插入其染色体进行修饰。sak 基因以 2 种形式整合 - （1）与其自身启动子相连和（2）融合到蛋白 A 基因的启动子 - 导致 SAK 的过表达。SAK 对人 plg 具有高度特异性，对鼠 plg 几乎没有活性。为了研究 SAK 在小鼠感染模型中的作用，将人 plg 转基因小鼠及其野生型对照小鼠通过静脉内接种在 SAK 产生方面存在差异的同基因金黄色葡萄球菌菌株。
与人 plg 转基因小鼠相比，表达 SAK 的菌株接种的小鼠死亡率明显降低，体重减轻减少，肾脏中的细菌负荷降低。与感染 SAK 缺乏菌株的转基因和野生型小鼠相比，败血症的严重程度没有差异。
结果表明，SAK 的表达随后激活 plg 可减轻金黄色葡萄球菌败血症的病程。
