Stockbauer K E, Grigsby D, Pan X, Fu Y X, Mejia L M, Cravioto A, Musser J M
Institute for the Study of Human Bacterial Pathogenesis, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3128-33. doi: 10.1073/pnas.95.6.3128.
In many countries, M1 strains of the human pathogenic bacterium group A Streptococcus are the most common serotype recovered from patients with invasive disease episodes. Strains of this serotype express an extracellular protein that inhibits complement [streptococcal inhibitor of complement (Sic)] and is therefore believed to be a virulence factor. Comparative sequence analysis of the 915-bp sic gene in 165 M1 organisms recovered from diverse localities and infection types identified 62 alleles. Inasmuch as multilocus enzyme electrophoresis and pulsed-field gel electrophoresis previously showed that most M1 organisms represent a distinct streptococcal clone, the extent of sic gene polymorphism was unexpected. The level of polymorphism greatly exceeds that recorded for all other genes examined in serotype M1 strains. All insertions and deletions are in frame, and virtually all nucleotide substitutions alter the amino acid sequence of the Sic protein. These molecular features indicate that structural change in Sic is mediated by natural selection. Study of 70 strains recovered from two temporally distinct epidemics of streptococcal infections in the former East Germany found little sharing of Sic variants among strains recovered in the different time periods. Taken together, the data indicate that sic is a uniquely variable gene and provide insight into a potential molecular mechanism contributing to fluctuations in streptococcal disease frequency and severity.
在许多国家，人类致病性细菌A群链球菌的M1菌株是侵袭性疾病发作患者中最常分离出的血清型。该血清型菌株表达一种抑制补体的细胞外蛋白[链球菌补体抑制剂（Sic）]，因此被认为是一种毒力因子。对从不同地点和感染类型分离出的165株M1菌株中915 bp的sic基因进行比较序列分析，鉴定出62个等位基因。鉴于多位点酶电泳和脉冲场凝胶电泳先前表明大多数M1菌株代表一个独特的链球菌克隆，sic基因多态性的程度出乎意料。多态性水平大大超过了血清型M1菌株中检测的所有其他基因的记录水平。所有插入和缺失均在阅读框内，几乎所有核苷酸替换都会改变Sic蛋白的氨基酸序列。这些分子特征表明Sic的结构变化是由自然选择介导的。对从前东德两次时间上不同的链球菌感染流行中分离出的70株菌株的研究发现，不同时间段分离出的菌株之间很少共享Sic变体。综合来看，这些数据表明sic是一个独特的可变基因，并为导致链球菌疾病频率和严重程度波动的潜在分子机制提供了见解。
