MINING THE ORAL MICROBIOME FOR NOVEL GLYCAN-BINDING MOLECULES

挖掘口腔微生物组中的新型聚糖结合分子

• 批准号: 8985451
• 负责人: Stefan Hans-Klaus Ruhl
• 金额: $ 33.37万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-05 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8985451
• 关键词: Adhesions; Affinity; Animals; Bacteria; Bacterial Adhesins; Bacterial Adhesion; Bacterial Polysaccharides; Binding; Binding Proteins; Bioinformatics; Biological; Carbohydrates; Cell surface; Communities; Dental; Detection; Environment; Exhibits; Foundations; Funding; Genomic approach; Genomics; Glycoproteins; Goals; Gram-Positive Bacteria; Grant; Habitats; Health; Human; Lectin; Ligand Binding; Mammals; Mediating; Medical; Microbial Biofilms; Mining; Mouth Diseases; Mucous body substance; N-glycolylneuraminic acid; Nature; Oral; Oral cavity; Oral health; Play; Polysaccharides; Property; Proteins; Recombinant DNA; Recombinants; Role; Salivary; Sampling; Sampling Studies; Serine; Specificity; Structure; Surface; Systemic disease; Techniques; Work; collaboratory; forging; member; novel; oral bacteria; oral biofilm; oral microbiome; receptor; research study; tool; tooth surface

DESCRIPTION (provided by applicant): In the oral environment, interactions between lectin-like adhesions on oral bacteria and complementary glycan recognition motifs on oral host cell and tooth surfaces and on the surfaces of other oral bacteria play important roles for initial bacterial colonization and the subsequent formation of multi-species biofilms that have the potential to turn into pathogenic habitats causing dental, oral, and perhaps systemic disease. Considering (a) the multitude of bacterial species identified in oral biofilms, (b) the rich diversty of glycans found on salivary glycoproteins, and (c) the innumerable glycan motifs expressed on the surface of other bacteria, it is likely that many more unidentified lectin-like bacterial adhesns exist in the oral microbiome, beyond the few ones currently known. Once identified, those bacterial lectin-like adhesins, many of which presumably will exhibit novel glycan-binding specificities, can be forged by recombinant DNA techniques into highly specific tools for the detecting and localization of corresponding glycan receptor structures. The overall objective of this application is to mine the oral microbiomes of humans and other mammals for novel glycan- binding bacterial adhesions by using glycan-functionalized targeted probes. Here, we focus on one well-characterized class of bacterial adhesions, the serine-rich repeat (SRR) proteins of Gram- positive bacteria. By identifying a novel set of glycan-binding proteins with unique ligand-binding properties, we aim to demonstrate as a proof of principle that it will become feasible to expand the range of currently available glycan-binding probes enormously. The specific aims of the project are to 1. Isolate SRR adhesion-bearing bacteria from the oral cavity of humans and other mammalian species that bind specifically to host sialoglycans containing 4- or 9-O-acetylated forms of N-acetyl and N-glycolylneuraminic acid. 2. Isolate SRR adhesin-bearing bacteria from human oral biofilms that bind specifically to bacterial polysaccharide receptors containing the unusual lectin-recognition motifs (Rhaα1-2Rha and Galα1- 6Glc). 3. Use bioinformatics to identify novel glycan-binding regions in SRR proteins, and use bacterial genomics to generate recombinant glycan-binding probes for detection of a diverse set of glycans.

描述（应用程序提供）：在口腔环境中，口腔细菌和互补的聚糖识别型在口腔宿主细胞和牙齿表面上以及其他口腔细菌的表面上的相互作用在最初细菌殖民的最初细菌和随后形成的多种习惯形成中，该习惯可能会变成多个习惯，以使其成为多型疾病的形成，以便于 疾病。考虑（a）口服生物膜中鉴定出的多种细菌物种，（b）在唾液糖蛋白上发现的聚糖的丰富度，以及（c）在其他细菌表面上表达的无数类血糖基序，可能会在其他未知的细菌粘附素中存在于其他细菌的表面上，超越了几个人，几乎没有一个人。一旦鉴定出，这些细菌讲授的粘合剂（大概许多可能会表现出新型的聚糖结合规格）可以通过重组DNA技术锻造成高度特异性的工具，以检测和定位相应的聚糖受体结构。该应用的总体目的是通过使用聚糖官能化的靶向问题来挖掘新型聚糖结合细菌粘合剂的人类和其他哺乳动物的口腔微生物组。在这里，我们专注于一类良好的细菌粘合剂，即革兰氏阳性细菌富含丝氨酸的重复（SRR）蛋白。通过确定具有独特配体结合特性的一组新型的聚糖结合蛋白，我们旨在证明原则的证明，可以极大地扩大当前可用的聚糖结合问题的范围是可行的。该项目的具体目的是1。分离的SRR粘附细菌与人类和其他哺乳动物物种的含符合性细菌，这些细菌与含有4或9-O乙酰化形式的N-乙酰基和N-乙酰基因尿氨基酸的唾液聚糖特异性结合。 2。与人口腔生物膜分离出含有粘合剂的细菌，这些细菌特异性与含有不寻常的讲座识别基序（RHAα1-2RHA和GALα1-6GLC）的细菌多糖受体结合。 3。使用生物信息学识别SRR蛋白中的新型聚糖结合区域，并使用细菌基因组学来产生重组聚糖结合问题，以检测一组潜水者的聚糖。