Interactions of Streptococcus mutans in Supragingival Biofilms

龈上生物膜中变形链球菌的相互作用

• 批准号: 10424695
• 负责人: Justin Ray Kaspar
• 金额: $ 15.75万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10424695
• 关键词: Adult; Appearance; Bacteria; Behavior; Biological Assay; Caries prevention; Characteristics; Child; Chronic Disease; Common Core; Communities; Confocal Microscopy; Data; Data Collection; Data Set; Dental caries; Development; Disease; Future; Gene Expression; Gene Expression Profile; Genes; Goals; Growth; Health; In Vitro; Maintenance; Measurement; Mechanics; Metabolic; Microbe; Microbial Biofilms; Mind; Mutation; Oral; Oral cavity; Oral health; Organism; Pathway interactions; Pattern; Process; Proteomics; Research; Research Personnel; Research Project Grants; Streptococcus; Streptococcus mutans; Testing; Tooth structure; career; commensal bacteria; design; differential expression; dysbiosis; fitness; gene discovery; gene product; indexing; interest; metatranscriptomics; microbiome; microbiome research; microorganism interaction; mutant; novel; oral bacteria; oral biofilm; oral microbiome; oral streptococci; pathogen; polymicrobial biofilm; prevent; programs; response; therapeutic target; tooth surface; transcriptome sequencing

PROJECT SUMMARY / ABSTRACT The microbes that inhabit oral biofilms attached to the tooth’s surface are constantly involved in interactions with other microbes that impact their ability to survive and grow within their niche. Streptococcus mutans, a primary driver of dental caries (tooth decay) development, forms rotund microcolonies on the surfaces of teeth that are in contact with other commensal bacteria, particularly health-associated Streptococcus species that encode mechanisms to deter S. mutans emergence and initiation of the cariogenic cycle. Outgrowth of S. mutans leads to ecological shifts within the oral microbiome community, reducing the proportions of health- associated streptococci and instead promoting the outgrowth of other acidogenic and aciduric bacteria that then further drive the disease (caries) process. Therefore, describing the initial interactions that occur between S. mutans and commensals is of critical need in the field of oral health to begin understanding factors that influence S. mutans establishment, persistence and outgrowth. Discovering gene(s) and/or pathway(s) that could serve as potential therapeutic targets to thwart the appearance of Sm while keeping the normal, protective flora intact remains a favorable strategy towards caries prevention and overall maintenance of good oral health. Recently, our group described a novel gene expression pattern within S. mutans when it was grown in mixed-species cultures with health-associated streptococci. Interestingly, this gene expression pattern was consistent with multiple Streptococcus species, suggesting that this may be a common S. mutans- encoded response to these competitors. Our central hypothesis is that the mixed-species gene expression pattern provides a fitness benefit to S. mutans during the early stages of biofilm establishment and allows S. mutans to compete with health-associated commensals, particularly streptococci. Our objective is to first fully describe the S. mutans gene expression pattern during mixed-species growth with different groups of oral bacteria not currently tested, including health-associated non-Streptococcus species and disease (caries)- associated species. This will allow us to determine if the gene expression pattern observed previously is unique to health-associated streptococci or common during all S. mutans mixed-species interactions. We will then aim to determine if differentially-expressed genes, particularly up-regulated S. mutans genes previously identified and pre-selected through collected preliminary RNA-Seq data, provide a fitness benefit to S. mutans during mixed-species growth and whether these gene(s)/gene product(s) could serve as future therapeutic targets. We hypothesize that several S. mutans genes will emerge that will significantly modify S. mutans fitness in mixed-species interactions and/or significantly alter Sm rotund microcolony formation which are critical for the caries disease process. Together, these aims will advance our understanding of how S. mutans responds to intermicrobial competition, and whether we can leverage these interactions to design new strategies to prevent S. mutans emergence within the oral microbiome.

项目摘要/摘要 附着在牙齿表面的口腔生物膜中的微生物不断参与相互作用 与其他影响它们在其利基内生存和生长的能力的微生物。变形链球菌，一种 龋齿(龋齿)发展的主要驱动力，在牙齿表面形成圆形微菌落 与其他共生细菌接触，特别是与健康相关的链球菌 编码机制，以阻止变形链球菌的出现和启动致龋性循环。S. 变形杆菌导致口腔微生物群落内的生态变化，降低了健康的比例- 而是促进其他产酸和耐酸细菌的生长，这些细菌 然后进一步推动疾病(龋齿)进程。因此，描述在以下情况下发生的初始交互 变形链球菌和共生菌在口腔健康领域是至关重要的，以开始了解 影响变形链球菌的建立、持续和生长。发现基因(S)和/或途径(S) 可以作为潜在的治疗靶点，在保持正常的同时阻止Sm的出现， 完整的保护性菌群仍然是预防龋病和全面维护良好的有利战略 口腔健康。最近，我们的团队描述了一种新的基因表达模式，在变形链球菌中 在与健康相关的链球菌的混合物种培养中生长。有趣的是，这种基因表达模式 与多种链球菌一致，提示这可能是一种常见的变形链球菌- 对这些竞争对手的编码响应。我们的中心假设是混合物种的基因表达 模式在生物膜形成的早期阶段为变形链球菌提供了一种健康的益处，并允许S。 变形杆菌与健康相关的共生菌，特别是链球菌竞争。我们的目标是首先充分 描述变形链球菌在不同口腔群体混合生长过程中的基因表达模式 目前没有测试的细菌，包括与健康相关的非链球菌物种和疾病(龋齿)- 相关物种。这将使我们能够确定之前观察到的基因表达模式是否 这是与健康相关的链球菌所特有的，或在所有变形链球菌的混合种间相互作用中常见。我们会 然后旨在确定差异表达的基因，特别是以前上调的变形链球菌基因 通过收集的初步RNA-Seq数据进行鉴定和预选，为变形链球菌提供适合性好处 在混合物种生长过程中，这些基因(S)/基因产物(S)是否可以作为未来的治疗药物 目标。我们假设将会出现几个变形链球菌基因，它们将显著改变变形链球菌。 适应混合物种的相互作用和/或显著改变Sm圆形微集落的形成，这是 对龋病过程至关重要。综合起来，这些目标将促进我们对变形链球菌如何 应对微生物间的竞争，以及我们是否可以利用这些相互作用来设计新的 防止变形链球菌在口腔微生物群中出现的策略。