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。 细胞壁多糖23 被 Ga1/Ga1Nac 凝集素识别的链球菌菌株 内氏放线菌已被分离并在结构上 特点。 这些多糖构成五种结构 每种类型均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端对端连接 磷酸核糖醇。 凝集素对这些分子的识别取决于 类似宿主的二糖基序，Ga1beta1-3Ga1NAc 或 Ga1NAcbeta1-3Ga1，存在于每个重复单元内。 相比之下， 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。 不同受体多糖结构密切相关 以及抗体和凝集素探针的特异性 分子，为开发提供了一个有吸引力的系统 设计特定多糖的分子生物学方法。 此功能是该项目的目标，可能有助于 受体生物学作用的改进定义 多糖在口腔定植以及发育中的作用 疫苗开发的新策略。 目前的研究重点是 受体多糖基因簇的鉴定。 这涉及转座子的分离和表征 表现出与特定的反应性改变的突变体 抗多糖抗体。 进一步的分子表征是 也在鉴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。