Oligino L, Fives-Taylor P
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, College of Medicine, University of Vermont, Burlington 05405.
Infect Immun. 1993 Mar;61(3):1016-22. doi: 10.1128/iai.61.3.1016-1022.1993.
A Streptococcus parasanguis adhesin that blocks the attachment of S. parasanguis FW213 to saliva-coated hydroxyapatite (SCHA) has been purified. Previous work demonstrated that the attachment of FW213 to SCHA is mediated by fimbriae and that one component associated with fimbriae is a 36-kDa protein (FimA) that reacts with antifimbria serum in Western blots (immunoblots) and is not present in afimbriated mutants. To obtain amounts of FimA sufficient for adhesion blocking assays, we cloned the gene coding for FimA into an Escherichia coli T7 overexpression system. The resulting strain produced large amounts of FimA, as much as 50% of the total cell protein. FimA was purified by elution from sodium dodecyl sulfate-polyacrylamide gels, and its native conformation was reestablished by sodium dodecyl sulfate removal, resolubilization in guanidine hydrochloride, and 50-fold dilution. Some refolded FimA aggregated into dimers and trimers. Preincubation of SCHA with 100 micrograms of purified, renatured FimA per ml blocked 85% of the binding of FW213. The FimA-SCHA complex was quite stable and could be washed continuously for at least 2 h with only a slight loss of FimA blocking activity. When FimA was added to preformed bacterium-SCHA complexes, it displaced 40% of the bacteria already bound to SCHA. The results suggest that FimA is an adhesin with a high substrate affinity and may prove useful in the development of a therapeutic agent for the prevention of plaque formation and endocarditis initiated by the sanguis streptococci.
一种能阻断副血链球菌FW213附着于唾液包被的羟基磷灰石(SCHA)的副血链球菌黏附素已被纯化。先前的研究表明,FW213与SCHA的附着是由菌毛介导的,并且与菌毛相关的一种成分是一种36 kDa的蛋白质(FimA),它在蛋白质免疫印迹(免疫印迹)中与抗菌毛血清发生反应,且不存在于无菌毛突变体中。为了获得足以进行黏附阻断试验的FimA量,我们将编码FimA的基因克隆到大肠杆菌T7过表达系统中。所得菌株产生了大量的FimA,高达总细胞蛋白的50%。通过从十二烷基硫酸钠 - 聚丙烯酰胺凝胶上洗脱来纯化FimA,并通过去除十二烷基硫酸钠、在盐酸胍中复溶以及50倍稀释来重新建立其天然构象。一些复性的FimA聚集成二聚体和三聚体。每毫升含100微克纯化的、复性的FimA与SCHA预孵育可阻断85%的FW213结合。FimA - SCHA复合物相当稳定,并且可以连续洗涤至少2小时,FimA阻断活性仅有轻微损失。当将FimA添加到预先形成的细菌 - SCHA复合物中时,它能取代已与SCHA结合的40%的细菌。结果表明,FimA是一种具有高底物亲和力的黏附素,可能在开发预防由血链球菌引发的牙菌斑形成和心内膜炎的治疗剂方面有用。