Jeng Arthur, Sakota Varja, Li Zhongya, Datta Vivekananda, Beall Bernard, Nizet Victor
Department of Pediatrics, Division of Pediatric Infectious Diseases, University of California, San Diego 92093, USA.
J Bacteriol. 2003 Feb;185(4):1208-17. doi: 10.1128/JB.185.4.1208-1217.2003.
The group A Streptococcus (GAS) sof gene encodes the serum opacity factor protein, which is capable of opacifying mammalian sera and binding at least two host proteins, fibronectin and fibrinogen. The sof gene exists in approximately 50% of clinical isolates, and there is a classical association of so-called nephritogenic strains with the opacity factor-positive phenotype. In both a type emm49 strain and a type emm12 strain, the sequences upstream of the 5' end of sof and downstream of the putative terminator were determined to be nearly identical to a region in the M type 1 genome approximately 10 kb upstream of the emm1 gene. This close genetic linkage is likely reflected in the strict correlation of opacity factor phenotype with specific emm genotypes. A new fibronectin-binding protein gene, sfbX, was discovered immediately downstream of sof in emm12 and emm49 strains and in several other sof-positive strains. The sof and sfbX genes were found to be expressed on the same transcription unit, which was correlated with the putative promoter and rho-independant terminator sequences that flank these two genes. The sfbX genes from different emm types are predicted to encode approximately 650-residue surface-bound proteins sharing 89 to 92% sequence identity. SfbX residues approximately 1 to 480 are not highly similar to those of other known proteins, with the closest match being the Staphylococcus aureus coagulase protein. The remaining portions of these proteins (residues 481 to 650) contain four putative fibronectin-binding repeats highly similar to those of other streptococcal fibronectin-binding proteins and a potential LP(X)SG cell wall anchor motif. Targeted in-frame allelic-exchange mutagenesis, complementation, and heterologous-expression studies found that serum opacification is encoded by sof alone and that sfbX encodes a fibronectin-binding function. A recombinant SfbX protein was found to bind immobilized fibronectin and to partially inhibit GAS adherence to fibronectin. The sfbX gene was found to be present only in sof-positive strains, and together these genes could influence the spectrum of tissues colonized by sof-positive GAS.
A群链球菌（GAS）的sof基因编码血清混浊因子蛋白，该蛋白能够使哺乳动物血清变混浊，并能结合至少两种宿主蛋白，即纤连蛋白和纤维蛋白原。sof基因存在于约50%的临床分离株中，所谓的致肾炎菌株与混浊因子阳性表型存在经典关联。在一株emm49型菌株和一株emm12型菌株中，sof 5'端上游和推定终止子下游的序列被确定与M1型基因组中emm1基因上游约10 kb处的一个区域几乎相同。这种紧密的遗传连锁可能反映在混浊因子表型与特定emm基因型的严格相关性上。在emm12和emm49菌株以及其他一些sof阳性菌株中，在sof下游紧邻处发现了一个新的纤连蛋白结合蛋白基因sfbX。发现sof和sfbX基因在同一转录单元上表达，这与位于这两个基因两侧的推定启动子和rho非依赖性终止子序列相关。预测来自不同emm类型的sfbX基因编码约650个残基的表面结合蛋白，序列同一性为89%至92%。SfbX约1至480位残基与其他已知蛋白的残基相似度不高，最接近的匹配是金黄色葡萄球菌凝固酶蛋白。这些蛋白的其余部分（481至650位残基）包含四个推定的纤连蛋白结合重复序列，与其他链球菌纤连蛋白结合蛋白的重复序列高度相似，以及一个潜在的LP(X)SG细胞壁锚定基序。靶向框内等位基因交换诱变、互补和异源表达研究发现，血清混浊仅由sof编码，而sfbX编码纤连蛋白结合功能。发现重组SfbX蛋白能结合固定化的纤连蛋白，并部分抑制GAS对纤连蛋白的黏附。发现sfbX基因仅存在于sof阳性菌株中，这些基因共同作用可能会影响sof阳性GAS定殖的组织范围。
