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

基本信息

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
项目类别：
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

项目摘要

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）：除了对口腔健康的许多其他贡献中，唾液有助于通过促进无害共生细菌促进定植的多种口腔生物膜微生物群中的生态平衡。由于口腔是对胃肠道和呼吸道的致病微生物的入口，因此存在合法的利益，以解剖与被假定的外生病原体绑定的唾液相互作用的唾液成分。初步数据表明，在结构表现或取代唾液酸对唾液糖蛋白上的结构表现或取代时，存在额外的复杂性，这些唾液糖蛋白可能会影响粘合蛋白介导的细菌结合，共同口服链霉菌和外肠外或分型病原体。 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病原体，例如幽门螺杆菌或肺炎链球菌。我们假设o-乙酰基的唾液酸取代会影响链球菌结合。预计该结果将使某些Viridans链球菌的令人惊讶的狭窄组织和宿主的tropism散发出更多的启示，其中某些链球菌仅在人类口腔内壮成长。鉴定细菌与唾液酸结合的结构要求不仅与唾液和对口腔疾病的易感性有关，例如龋齿和牙周炎，而且还可以很容易地用于致病性微生物与其他身体分泌物与其他分泌物的相互作用，并在呼吸道上杂乱无章的上皮性上皮和Gentirepital和Gentir digestial，gentactial和Gentir digactial，gentactial和Gentirapitial和Gentractiate。此外，一旦确定了某些微生物粘附素的确切的唾液酸识别基序，就可以将碳水化合物类似物作为药物设计，以防止不希望的细菌定植。该项目的具体目的是：1。定义如何在2-D唾液糖蛋白酶成员之间分布9-乙酰化的唾液酸。 2。确定通过相应的粘附素识别的唾液酸的结构亚型，并证明唾液酸的9-o-乙酰化决定链球菌与唾液糖蛋白的结合。这些目标将通过糖基学和蛋白质组学方法的结合来实现。