Rubens C E, Wessels M R, Kuypers J M, Kasper D L, Weiser J N
Department of Pediatrics, University of Washington, Children's Hospital and Medical Center, Seattle 98105.
Semin Perinatol. 1990 Aug;14(4 Suppl 1):22-9.
Molecular biology has provided new technology for evaluating the traits of bacterial pathogens that are important in the pathogenesis of infections. The ability to derive isogenic strains that differ by a single trait provides a powerful tool for investigating the interaction of a putative virulence factor with the host at any of the various steps in pathogenesis. Recombinant DNA techniques afford the opportunity to clone the genes involved in the biosynthesis of a particular virulence factor. Once the gene(s) are cloned, a vast amount of information can be learned about their composition, structure, and regulation, and similarity with genes in other organisms. Understanding the molecular biology of a virulence factor also provides information about potential targets for future therapies and preventive modalities. The molecular analysis of two virulence factors from the type III group B streptococcus has been reviewed to provide specific examples of how these techniques can be used. The data has shown that the capsular polysaccharide is an essential factor in GBS virulence. The structural influence of sialic acid on the capsule plays a major role in its virulence properties. The importance of the capsule has been tested in several assays to identify its role in pathogenesis. Its primary role appears to be evading host phagocytic mechanisms, but it does not appear to be essential in the vascular response observed during GBS sepsis. Using the isogenic strains, we have also learned that the capsule does not mask a fibronectin receptor on GBS. In contrast to the capsule, the beta-hemolysin of GBS does not appear to be essential for systemic disease once the organism has invaded. Its role in the initial invasive steps in GBS pathogenesis has not been tested, but the availability of isogenic mutants in beta-hemolysin production will allow this question to be answered once the model systems are available.(ABSTRACT TRUNCATED AT 250 WORDS)
分子生物学为评估在感染发病机制中起重要作用的细菌病原体特征提供了新技术。获得仅在单一性状上存在差异的同基因菌株的能力,为研究假定的毒力因子在发病机制的各个步骤中与宿主的相互作用提供了强大工具。重组DNA技术为克隆参与特定毒力因子生物合成的基因提供了机会。一旦基因被克隆,就可以了解到关于它们的组成、结构、调控以及与其他生物体中基因的相似性等大量信息。了解毒力因子的分子生物学也为未来的治疗和预防方法提供了潜在靶点的信息。本文综述了对B族链球菌III型两种毒力因子的分子分析,以提供这些技术如何应用的具体实例。数据表明,荚膜多糖是B族链球菌毒力的一个重要因素。唾液酸对荚膜的结构影响在其毒力特性中起主要作用。荚膜的重要性已在多项试验中得到验证,以确定其在发病机制中的作用。其主要作用似乎是逃避宿主的吞噬机制,但在B族链球菌败血症期间观察到的血管反应中似乎并非必不可少。利用同基因菌株,我们还了解到荚膜不会掩盖B族链球菌上的纤连蛋白受体。与荚膜不同,一旦病原体侵入,B族链球菌的β - 溶血素似乎对全身性疾病并非必不可少。其在B族链球菌发病机制初始侵入步骤中的作用尚未得到验证,但一旦有了模型系统,β - 溶血素产生同基因突变体的可得性将使这个问题得以解答。(摘要截短至250字)