Interactions of Streptococcus mutans in Supragingival Biofilms

项目总结/摘要 附着在牙齿表面的口腔生物膜中的微生物不断地参与相互作用 影响它们在生态位内生存和生长的能力。变形链球菌a 龋齿（蛀牙）发展的主要驱动因素，在牙齿表面形成圆形小菌落 与其他肠道细菌接触，特别是与健康相关的链球菌， 编码阻止S.变形菌的出现和致龋周期的开始。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， 与链球菌相关，而是促进其他产酸和耐酸细菌的生长， 然后进一步推动疾病（龋齿）进程。因此，描述发生在 S.口腔健康领域迫切需要了解口腔变异体和细菌的致病因素，从而开始了解 影响S。变形菌的建立、持续和生长。发现基因和/或途径， 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， 完整的保护性植物群仍然是预防龋齿和整体维持良好的 口腔健康.最近，我们的小组描述了一个新的基因表达模式，在S。变异人的时候， 与健康相关的链球菌混合培养。有趣的是，这种基因表达模式 与多种链球菌属一致，表明这可能是一种常见的链球菌。变异体， 对这些竞争对手的回应。我们的中心假设是混合物种的基因表达 模式为S提供适应性益处。在生物膜建立的早期阶段，允许S. 变形杆菌与健康相关的细菌，特别是链球菌竞争。我们的目标是首先全面 描述S。不同口腔黏膜混合生长过程中变形杆菌基因的表达模式 目前未检测的细菌，包括与健康相关的非链球菌菌种和疾病（龋齿）- 相关物种这将使我们能够确定先前观察到的基因表达模式是否是 独特的健康相关链球菌或常见的所有S。变种人混合物种的相互作用。我们将 然后旨在确定差异表达的基因，特别是上调的S.变异基因以前 通过收集的初步RNA-Seq数据鉴定和预选，为S.变形 以及这些基因/基因产物是否可以作为未来的治疗药物 目标的我们假设几个S.变异基因将会出现，这将显著改变S。变形 适合混合物种的相互作用和/或显着改变Sm圆形小菌落的形成， 对于龋齿疾病过程至关重要。总之，这些目标将促进我们对S。变形 对微生物间竞争的反应，以及我们是否可以利用这些相互作用来设计新的 预防S.口腔微生物组中出现的变形菌。

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.