Akesson P, Sjöholm A G, Björck L
Department of Cell and Molecular Biology, Lund University, Sweden.
J Biol Chem. 1996 Jan 12;271(2):1081-8. doi: 10.1074/jbc.271.2.1081.
The human pathogen Streptococcus pyogenes possesses a chromosomal region, the mga regulon, that contains co-regulated genes important to the virulence of these bacteria. A novel gene located in the mga regulon of a S. pyogenes strain of serotype M1 was cloned and sequenced. It translates into a protein of 305 amino acid residues, including a signal sequence of 32 amino acids and a central region consisting of three tandem repeats. The sequence represents a novel structure with no significant homology to any previously published sequence. The protein was purified from the streptococcal culture media where it is present in substantial amounts. Affinity chromatography of human plasma on Sepharose coupled with the protein specifically absorbed two plasma proteins which were identified as clusterin and histidine-rich glycoprotein (HRG). The interactions between the streptococcal protein and the plasma proteins were further characterized using purified clusterin and HRG. Inhibition experiments indicated that they have affinity for overlapping or closely located sites in the streptococcal protein. Both clusterin and HRG are regulators of the membrane attack complex (C5b-C9) of complement. When the streptococcal protein was added to serum, complement-mediated lysis of sensitized sheep erythrocytes and guinea pig erythrocytes was inhibited. In addition, the streptococcal protein was incorporated into C5b-C9 in serum, indicating the location of its action. The name, protein SIC, streptococcal inhibitor of complement-mediated lysis, is therefore suggested for this novel protein. The occurrence of protein SIC and its gene was investigated in a collection of S. pyogenes strains comprising 55 different M serotypes. Only M1 and M57 strains were positive in this screening, indicating that protein SIC could be a virulence determinant. Thus, during recent years, the M1 serotype has been connected with a world-wide increase of severe and toxic S. pyogenes infections.
人类病原体化脓性链球菌拥有一个染色体区域，即mga调控子，其中包含对这些细菌毒力至关重要的共同调控基因。克隆并测序了位于血清型M1的化脓性链球菌菌株mga调控子中的一个新基因。它编码一个由305个氨基酸残基组成的蛋白质，包括一个32个氨基酸的信号序列和一个由三个串联重复序列组成的中心区域。该序列代表一种新结构，与任何先前发表的序列均无显著同源性。该蛋白质是从链球菌培养基中大量存在的地方纯化得到的。用与该蛋白质特异性结合的琼脂糖凝胶对人血浆进行亲和层析，吸附了两种血浆蛋白，分别鉴定为簇集素和富含组氨酸的糖蛋白（HRG）。使用纯化的簇集素和HRG进一步表征了链球菌蛋白与血浆蛋白之间的相互作用。抑制实验表明，它们对链球菌蛋白中重叠或紧密相邻的位点具有亲和力。簇集素和HRG都是补体膜攻击复合物（C5b - C9）的调节因子。当将链球菌蛋白加入血清中时，补体介导的致敏绵羊红细胞和豚鼠红细胞的裂解受到抑制。此外，链球菌蛋白被整合到血清中的C5b - C9中，表明了其作用位点。因此建议将这种新蛋白质命名为蛋白质SIC，即补体介导裂解的链球菌抑制剂。在一组包含55种不同M血清型的化脓性链球菌菌株中研究了蛋白质SIC及其基因的存在情况。在该筛选中只有M1和M57菌株呈阳性，表明蛋白质SIC可能是一种毒力决定因素。因此，近年来，M1血清型与全球范围内严重且有毒的化脓性链球菌感染的增加有关。
