Veterans Affairs Medical Center, Memphis, TN 38104, United States.
Microbes Infect. 2011 Apr;13(4):413-8. doi: 10.1016/j.micinf.2010.12.008. Epub 2011 Jan 15.
The binding of fibrinogen to M-related protein (Mrp) is known to contribute to the ability of Streptococcus pyogenes to evade phagocytosis by preventing the deposition of complement on the streptococcal surface. The objectives of this investigation were to map the common fibrinogen-binding domain of Mrp and to determine if this domain has a therapeutic potential to enhance phagocytosis of S. pyogenes in human blood. Using a series of recombinant, truncated proteins of Mrp, two fibrinogen-binding domains (FBD) were mapped. FBD1 was contained within amino acid residues 1-55 of Mrp and FBD2 within residues 81-138. FBD2 is found in all Mrp sequenced to date whereas FBD1 is not. Both FBD1 and FBD2 peptides but not a control peptide blocked the binding of fibrinogen to S. pyogenes and promoted phagocytosis of the streptococci in human blood. The data support the hypothesis that the binding of fibrinogen by S. pyogenes is centrally involved in their resistance to phagocytosis in human blood and suggest that treatments that interfere with the binding of fibrinogen to S. pyogenes may help in fighting infections by these organisms.
纤维蛋白原与 M 相关蛋白 (Mrp) 的结合被认为有助于化脓性链球菌逃避吞噬作用，方法是防止补体在链球菌表面沉积。本研究的目的是绘制 Mrp 的常见纤维蛋白原结合域，并确定该域是否具有增强人血中化脓性链球菌吞噬作用的治疗潜力。使用一系列重组、截断的 Mrp 蛋白，绘制了两个纤维蛋白原结合域 (FBD)。FBD1 位于 Mrp 的残基 1-55 内，FBD2 位于残基 81-138 内。迄今为止，在所有测序的 Mrp 中都发现了 FBD2，而不是 FBD1。FBD1 和 FBD2 肽都能阻止纤维蛋白原与化脓性链球菌的结合，并促进人血中链球菌的吞噬作用，但对照肽则不能。这些数据支持这样一种假设，即纤维蛋白原与化脓性链球菌的结合在其对人血吞噬作用的抵抗中起着核心作用，并表明干扰纤维蛋白原与化脓性链球菌结合的治疗方法可能有助于对抗这些生物体的感染。
