MOLECULAR BIOLOGY OF STREPTOCOCCAL RECEPTOR POLYSACCHARIDES

链球菌受体多糖的分子生物学

• 批准号: 2456751
• 负责人: J O CISAR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2456751
• 关键词: Streptococcus; bacterial genetics; bacterial polysaccharides; carbohydrate receptor; gene mutation; glycosyltransferase; microorganism culture; molecular biology; oral bacteria; phosphoric ester; transposon /insertion element

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.

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。 草绿色链球菌， 启动牙齿表面的定殖，包括具有细胞的菌株 壁多糖是植物凝集素的受体分子， 其他口腔细菌 23个菌株的细胞壁多糖 由Ga 1/Ga 1 Nac凝集素识别的链球菌菌株 内氏放线菌的分离和结构 表征了 这些多糖构成五种结构 每种类型由稍微不同的六糖或七糖组成 通过磷酸二酯键或通过 磷酸核糖醇 凝集素对这些分子的识别依赖于 宿主样二糖基序，Ga 1 β 1 - 3Ga 1 NAc或 Ga 1 NAc β 1 - 3Ga 1，存在于每个重复单元内。 与此相反， 抗多糖抗体的反应可能涉及结构 与免疫隐性宿主样基序不同的特征。 不同受体多糖的密切相关结构 以及抗体和凝集素探针对这些的特异性 分子，为开发 分子生物学方法来设计特定的多糖。 这一能力是本项目的目标，可能有助于 对受体生物学作用的更好定义 多糖在口腔定植，也发展 疫苗开发的新策略。 目前的研究集中在 对受体多糖基因簇的鉴定。 这涉及到转座子的分离和鉴定 突变体表现出改变的与特异性 抗多糖抗体 进一步的分子表征是 还正在鉴定特定糖基转移酶的基因， 作为多糖决定因素的相关生物合成酶 结构