The Role of Salivary Mucin in Preventing Cariogenic Streptococcus Biofilm Formation

唾液粘蛋白​​在预防致龋链球菌生物膜形成中的作用

• 批准号: 8981283
• 负责人: Erica Shapiro Frenkel
• 金额: $ 4.05万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8981283
• 关键词: Acids; Affect; Anti-Bacterial Agents; Bacteria; Bacterial Physiology; Biochemistry; Childhood; Chronic; Coculture Techniques; Colony-forming units; Crohn' s disease; Cystic Fibrosis; Data; Defect; Defense Mechanisms; Dental Enamel; Dental caries; Development; Diagnostic; Dietary Sucrose; Disease; Epithelial; Extracellular Matrix; Gastrointestinal Diseases; Gene Expression Regulation; Genetic; Genetic Transcription; Glass; Glycoproteins; Goals; Growth; Host Defense; Human; Hydrogen Peroxide; Hydroxyapatites; Immune system; Invaded; Lead; Link; Lubrication; MUC5B gene; Metabolic; Microbe; Microbial Biofilms; Microbiology; Microscopy; Modeling; Mouth Diseases; Mucin 1 protein; Mucins; Mucous body substance; Oral; Oral cavity; Oral health; Pathogenesis; Peptides; Phenotype; Physiology; Play; Prevalence; Prevention; Production; Proline; Property; Public Health; RNA Sequences; Research; Reverse Transcription; Role; Salivary; Series; Serine; Streptococcus; Streptococcus mutans; Surface; Testing; Thick; Threonine; Time; Ulcerative Colitis; Vertebral column; Virulence; antimicrobial; base; clinically relevant; gastrointestinal; gene interaction; glycosylation; insight; microbial community; mutant; novel; oral bacteria; oral microbiome; organic acid; overexpression; pathogen; pathogenic bacteria; prevent; public health relevance; reproductive; research study; respiratory; salivary mucins; tooth surface; transcriptome sequencing

 DESCRIPTION (provided by applicant): Mucus acts as a protective barrier on wet epithelial surfaces in the body including the gastrointestinal and reproductive tracts. A main component of mucus are mucins, which give mucus its viscoelastic properties and is a key component of host defense at these epithelial interfaces. Altered mucin production has been linked to gastrointestinal diseases such as Crohn's disease and respiratory illnesses like cystic fibrosis, which highlights the importance of regulated mucin production. Although mucins role in gastrointestinal and respiratory illnesses has been well characterized, little is known about the connection between salivary mucins and common oral diseases such as dental caries. Cavities form when bacteria attach to and grow on tooth surfaces then produce organic acids as metabolic byproducts, which dissolve tooth enamel. Streptococcus mutans is the primary cavity-forming oral bacterium, therefore understanding the impact of salivary mucins on S. mutans physiology may significantly impact the development of new oral therapies. In this study we will use a combination of microbiology, biochemistry, genetic and microscopy experiments to understand how human MUC5B salivary mucins affect S. mutans gene regulation and interaction with competing bacterial species. Preliminary data for this study shows that MUC5B increases survival of Streptococcus sanguinis, a beneficial oral bacterium known to compete with S. mutans, therefore we hypothesize that MUC5B plays a key role in decreasing the prevalence of caries and maintaining a healthy oral microbial community. To test this hypothesis we will first characterize differences in S. mutans gene regulation in the presence of MUC5B to understand the mechanism underlying mucins' protective influence. Then, we will evaluate the effects of MUC5B on S. sanguinis attachment and biofilm formation. Once we have determined the effects of MUC5B on key parameters of S. mutans and S. sanguinis physiology independently, we will use a dual-species model to understand how MUC5B impacts the development of multispecies biofilms. The main goals of this study are to understand how MUC5B influences S. mutans gene regulation then to determine how these changes play a role in inter-species bacterial competition. These findings could lead to significant insights into the pathogenesis of caries formation that aid in the development of novel therapies or preventative strategies.

 描述（由申请方提供）：粘液作为体内湿上皮表面（包括胃肠道和生殖道）的保护屏障。粘液的主要成分是粘蛋白，其赋予粘液粘弹性，并且是这些上皮界面处的宿主防御的关键成分。改变的粘蛋白产生与胃肠道疾病如克罗恩病和呼吸道疾病如囊性纤维化有关，这突出了调节粘蛋白产生的重要性。 虽然粘蛋白在胃肠道和呼吸道疾病中的作用已经得到了很好的表征，但对唾液粘蛋白与常见口腔疾病如龋齿之间的联系知之甚少。当细菌附着并生长在牙齿表面时，就会形成蛀牙，然后产生有机酸作为代谢副产品，溶解牙釉质。变形链球菌是主要的口腔菌腔形成，因此了解唾液粘蛋白对变形链球菌的影响。变形菌生理学可能显著影响新口服疗法的发展。 在本研究中，我们将结合微生物学、生物化学、遗传学和显微镜实验来了解人类MUC5B唾液粘蛋白如何影响S。变形杆菌基因调控和与竞争细菌物种的相互作用。这项研究的初步数据表明，MUC5B增加了血链球菌的存活，血链球菌是一种有益的口腔细菌，已知与链球菌竞争。因此，我们假设MUC5B在降低龋齿患病率和维持健康的口腔微生物群落中起关键作用。为了检验这一假设，我们将首先描述S的差异。在MUC5B的存在下，对变形蛋白基因的调控进行研究，以了解粘蛋白保护作用的潜在机制。然后，我们将评估MUC5B对S.血吸虫附着和生物膜形成。一旦我们确定了MUC5B对S.和S. sanguinis生理学独立，我们将使用双物种模型来了解MUC5B如何影响多物种生物膜的发展。本研究的主要目的是了解MUC5B如何影响S。然后确定这些变化如何在种间细菌竞争中发挥作用。这些发现可能导致对龋齿形成的发病机制的重要见解，有助于开发新的治疗或预防策略。