MOLECULAR BIOLOGY OF STREPTOCOCCAL RECEPTOR POLYSACCHARIDES

口腔微生物定植涉及许多特定的 不同细菌之间的相互作用。绿色链球菌 开始在牙齿表面定植，包括带有细胞的菌株 壁多糖是凝集素的受体分子 其他口腔细菌。23菌株胞壁多糖的研究 GA1/Ga1Nac凝集素识别的链球菌 对内氏放线菌进行了分离和结构鉴定 特色化的。这些多糖组成了五种结构 每种类型都由略有不同的六糖或七糖组成 重复单元通过磷酸二酯键或通过 核糖醇磷酸盐。凝集素对这些分子的识别取决于 类宿主双糖基序，Ga1beta1-3Ga1NAc或 Ga1NAcbeta1-3Ga1，存在于每个重复单元中。相比之下， 抗多糖抗体的反应可能涉及结构 不同于免疫隐性寄主类模体的特征。 不同受体多糖密切相关的结构 以及抗体和凝集素探针对这些的特异性 分子，为开发一种具有吸引力的系统提供了 设计特定多糖的分子生物学方法。 这一能力，这是本项目的目标，可能有助于 关于受体生物学作用的改进定义 多糖类在口腔定植中的作用及其与肿瘤发育的关系 疫苗开发的新战略。目前的研究主要集中在 受体多糖基因簇的鉴定。 这涉及到转座子的分离和鉴定。 与特定基因发生反应性改变的突变体 抗多糖抗体。进一步的分子表征是 也在确定特定糖基转移酶的基因和 作为多糖决定因素的相关生物合成酶 结构。

Oral microbial colonization involves a number of specific interactions between different bacteria. Viridans streptococci that initiate colonization of the tooth surface include strains with cell wall polysaccharides that are receptor molecules for the lectins of other oral bacteria. The cell wall polysaccharides of 23 streptococcal strains that are recognized by the Ga1/Ga1Nac lectins of Actinomyces naeslundii have been isolated and structurally characterized. These polysaccharides constitute five structural types each composed of a somewhat different hexa- or heptasaccharide repeating unit linked end-to-end by phosphodiester bonds or through ribitol phosphate. Lectin recognition of these molecules depends on a host-like disaccharide motif, either Ga1beta1-3Ga1NAc or Ga1NAcbeta1-3Ga1, present within each repeating unit. In contrast, the reactions of antipolysaccharide antibodies may involve structural features that are distinct from the immunorecessive host-like motifs. The closely related structures of different receptor polysaccharides and the specificities of antibody and lectin probes for these molecules, provide an attractive system for development of a molecular biological approach to engineer specific polysaccharides. This capability, which is the goal of this project, may contribute to the improved definition of the biological role of receptor polysaccharides in oral colonization and also to the development of new strategies for vaccine development. Current studies are focused on identification of the gene clusters for receptor polysaccharides. This involves the isolation and characterization of transposon mutants that exhibit altered reactivity with specific antipolysaccharide antibodies. Further molecular characterization is also underway to identify genes for specific glycosyl tranferases and related biosynthetic enzymes that are determinants of polysaccharide structure.