Microbial Recognition of Sialic Acid Diversity in the Salivary Proteome

唾液蛋白质组中唾液酸多样性的微生物识别

• 批准号: 8487394
• 负责人: Stefan Hans-Klaus Ruhl
• 金额: $ 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: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487394
• 关键词: Acetylation; Adhesions; Animals; Applications Grants; Bacteria; Bacterial Adhesins; Benign; Binding; Biological Process; Bodily secretions; Capillary Electrophoresis; Carbon; Cells; Chemicals; Data; Dental caries; Disease; Epithelium; Equilibrium; Erythrocytes; Family; Fostering; Future; Gastrointestinal tract structure; Genital system; Glycoproteins; Goals; Health; Helicobacter pylori; Hemagglutination; Host Defense; Human; Individual; Infection; Infection prevention; Intervention; Investigation; Knowledge; Lectin; Light; Link; Lipids; Liquid substance; Mass Spectrum Analysis; Mediating; Methods; Molecular; Mouth Diseases; Mucous body substance; Natural Immunity; Nature; Neuraminidase; Oral; Oral cavity; Oral health; Outcome; Pathologic Processes; Periodontitis; Pharmaceutical Preparations; Physiological Processes; Polysaccharides; Positioning Attribute; Predisposition; Prevention; Process; Proteins; Proteome; Proteomics; Recombinants; Research; Respiratory System; Respiratory tract structure; Role; Saliva; Salivary; Salivary Proteins; Sialic Acids; Sialoglycoproteins; Specificity; Streptococcus; Streptococcus Viridans Group; Streptococcus gordonii; Streptococcus pneumoniae; Sugar Acids; Surface; Testing; Tissues; Tropism; Variant; Viral; Virus; Well in self; Work; bacterial adhesin receptor; base; carbohydrate analog; clinically relevant; commensal microbes; design; gastrointestinal; glycosylation; interest; member; microbial; microorganism; mutant; oral biofilm; oral commensal; oral infection; oral streptococci; pathogen; prevent; public health relevance; receptor; respiratory; tissue tropism; two-dimensional

DESCRIPTION (provided by applicant): Among many other contributions to oral health, saliva helps to maintain an ecological balance within the diverse oral biofilm microbiota through fostering colonization by harmless commensal bacteria. Because the oral cavity serves as a port of entry for pathogenic microorganisms to both gastrointestinal and respiratory tracts, legitimate interest exists to dissect salivary components that interact with commensal bacteria from those that are bound by putative extraoral pathogens. Preliminary data suggest that there exists additional not yet well understood complexity in the structural presentation or substitution of sialic acids on salivary glycoproteins that are likely to influence adhesin-mediated bacterial binding by both, commensal oral streptococci and extraoral pathogens. Considering that more than 40 different structural subtypes of sialic acids exist in nature and are known to mediate a wide variety of physiological and pathological processes, including recognition by viruses and other pathogens, thus far little work has been done to determine which structural sialic acid subtypes are present on glycoproteins in human saliva, and which are specifically recognized by oral commensal streptococci in comparison to sialic acid binding pathogens such as H. pylori or S. pneumoniae. We hypothesize that sialic acid substitution by O-acetyl groups influences streptococcal binding. The results are expected to shed additional light on the surprisingly narrow tissue and host tropism of certain viridans streptococci, of which some thrive exclusively within the human oral cavity. Identification of the structural requirements for bacterial binding to sialic acids will be relevant not only to saliva and susceptibility to oral diseases, such as caries and periodontitis, but may also be readily applied to the interaction of pathogenic microorganisms with other bodily secretions and mucous-covered epithelia in respiratory, digestive and genital tracts. Moreover, once the exact sialic acid recognition motifs for certain microbial adhesins are determined, it will become possible to design carbohydrate analogues as drugs to prevent colonization by undesired bacteria. The specific aims of the project are to: 1. Define how 9-O-acetylated sialic acids are distributed among members of the 2-D salivary glycoproteome. 2. Determine the structural subtypes of sialic acids recognized by the corresponding adhesins and demonstrate that 9-O-acetylation of sialic acids determines streptococcal binding to salivary glycoproteins. These aims will be achieved by a combination of glycobiological and proteomics methods.

描述（由申请人提供）：在对口腔健康的许多其他贡献中，唾液通过促进无害共生细菌的定植，有助于维持多样化口腔生物膜微生物群内的生态平衡。由于口腔是病原微生物进入胃肠道和呼吸道的入口，因此存在合法的兴趣来解剖与共生细菌相互作用的唾液成分，以及与假定的口外病原体结合的唾液成分。初步数据表明，唾液糖蛋白上唾液酸的结构呈现或取代还存在尚未充分理解的复杂性，这可能会影响共生口腔链球菌和口外病原体的粘附素介导的细菌结合。考虑到自然界中存在 40 多种不同的唾液酸结构亚型，并且已知其介导多种生理和病理过程，包括病毒和其他病原体的识别，迄今为止，几乎没有开展工作来确定人类唾液中糖蛋白上存在哪些结构唾液酸亚型，以及与唾液酸结合相比，哪些结构唾液酸亚型可以被口腔共生链球菌特异性识别 病原体，例如幽门螺杆菌或肺炎链球菌。我们假设唾液酸被 O-乙酰基取代会影响链球菌结合。预计这些结果将进一步揭示某些草绿色链球菌令人惊讶的狭窄组织和宿主向性，其中一些链球菌专门在人类口腔内繁殖。细菌与唾液酸结合的结构要求的鉴定不仅与唾液和对口腔疾病（如龋齿和牙周炎）的易感性有关，而且还可以很容易地应用于病原微生物与呼吸道、消化道和生殖道中其他身体分泌物和粘液覆盖上皮的相互作用。此外，一旦确定了某些微生物粘附素的准确唾液酸识别基序，就有可能设计碳水化合物类似物作为药物来防止不良细菌的定植。该项目的具体目标是： 1. 定义 9-O-乙酰化唾液酸如何在 2-D 唾液糖蛋白组成员之间分布。 2. 确定相应粘附素识别的唾液酸的结构亚型，并证明唾液酸的 9-O-乙酰化决定了链球菌与唾液糖蛋白的结合。这些目标将通过糖生物学和蛋白质组学方法的结合来实现。