Stålhammar-Carlemalm M, Stenberg L, Lindahl G
Department of Medical Microbiology, University of Lund, Sweden.
J Exp Med. 1993 Jun 1;177(6):1593-603. doi: 10.1084/jem.177.6.1593.
The group B Streptococcus, an important cause of invasive infections in the neonate, is classified into four major serotypes (Ia, Ib, II, and III) based on the structure of the polysaccharide capsule. Since the capsule is a known virulence factor, it has been extensively studied, in particular in type III strains, which cause the majority of invasive infections. Two cell surface proteins, alpha and beta, have also been studied in detail since they confer protective immunity, but these proteins are usually not expressed by type III strains. We describe here a cell surface protein, designated protein Rib (resistance to proteases, immunity, group B), that confers protective immunity and is expressed by most strains of type III. Protein Rib was first identified as a distinct 95-kD protein in extracts of a type III strain, and was purified to homogeneity from that strain. Rabbit antiserum to protein Rib was used to demonstrate that it is expressed on the cell surface of 31 out of 33 type III strains, but only on 1 out of 25 strains representing the other three serotypes. Mouse protection tests showed that antiserum to protein Rib protects against lethal infection with three different strains expressing this antigen, including a strain representing a recently identified high virulence type III clone. Protein Rib is immunologically unrelated to the alpha and beta proteins, but shares several features with the alpha protein. Most importantly, the NH2-terminal amino acid sequences of the Rib and alpha proteins are identical at 6 out of 12 positions. In addition, both protein Rib and the alpha protein are relatively resistant to trypsin (and Rib is also resistant to pepsin) and both proteins vary greatly in size between different clinical isolates. Finally, both protein Rib and the alpha protein exhibit a regular ladderlike pattern in immunoblotting experiments, which may reflect a repetitive structure. Taken together, these data suggest that the Rib and alpha proteins are members of a family of proteins with related structure and function. Since protein Rib confers protective immunity, it may be valuable for the development of a protein vaccine against the group B Streptococcus, an encapsulated bacterium.
B族链球菌是新生儿侵袭性感染的重要病因,根据多糖荚膜的结构可分为四种主要血清型(Ia、Ib、II和III)。由于荚膜是已知的毒力因子,因此已对其进行了广泛研究,尤其是在III型菌株中,该型菌株引起了大多数侵袭性感染。两种细胞表面蛋白,α和β,也已得到详细研究,因为它们具有保护性免疫,但这些蛋白通常不由III型菌株表达。我们在此描述一种细胞表面蛋白,命名为Rib蛋白(抗蛋白酶、免疫、B族),它具有保护性免疫,并且大多数III型菌株都能表达。Rib蛋白最初在一株III型菌株的提取物中被鉴定为一种独特的95-kD蛋白,并从该菌株中纯化至同质。用抗Rib蛋白的兔抗血清证明,它在33株III型菌株中的31株细胞表面表达,但在代表其他三种血清型的25株菌株中仅在1株中表达。小鼠保护试验表明,抗Rib蛋白的抗血清可保护小鼠免受三种表达该抗原的不同菌株的致死性感染,包括一株代表最近鉴定出的高毒力III型克隆的菌株。Rib蛋白与α和β蛋白在免疫上无关,但与α蛋白有几个共同特征。最重要的是,Rib蛋白和α蛋白的NH2末端氨基酸序列在12个位置中的6个位置相同。此外,Rib蛋白和α蛋白对胰蛋白酶都相对耐药(Rib蛋白对胃蛋白酶也耐药),并且这两种蛋白在不同临床分离株中的大小差异很大。最后,Rib蛋白和α蛋白在免疫印迹实验中均呈现规则的阶梯状模式,这可能反映了一种重复结构。综上所述,这些数据表明Rib蛋白和α蛋白是具有相关结构和功能的蛋白家族成员。由于Rib蛋白具有保护性免疫,它可能对开发针对B族链球菌(一种有荚膜的细菌)的蛋白疫苗具有重要价值。