Interspecies Streptococcal Antagonisms in Oral Biofilms

描述（由申请人提供）：候选人的背景是细菌遗传学，生物膜形成和细菌毒力。目前的目标是为独立科学家的职业生涯做准备，并开发牙齿生物膜中细菌相互作用的模型。职业目标是成为一名独立的口腔微生物生态学研究科学家，并成为排名学术教师。指导阶段将包括开发额外的技术技能，专题，教学和教学法，参与T32 MinnCResT计划，并在研讨会和会议上发表演讲。受到指导的阶段将包括与联合国大学的研究人员建立跨学科合作关系，这种合作关系将在独立阶段得到扩展，届时主要重点是完成拟议的研究。环境：该研究将在UMN牙科学院M.C. Herzberg博士的实验室进行，他是链球菌生物学方面的知名专家，特别是在表面粘附蛋白，生物膜发育和血链球菌心内膜炎的病理生理学方面。研究：变形链球菌在龋齿病因学中的作用已经得到了很好的研究。变形链球菌存在于牙菌斑中，有70多种细菌。事实上，变形链球菌相关微生物组的相互作用可能决定牙菌斑的蛀牙潜能。这些相互作用包括基因表达的调节、种间共聚集和生长抑制。我们假设口服链球菌的竞争部分是通过直接的物理相互作用和/或代谢信号影响拮抗或拮抗物种的毒力基因表达来实现的。我们将模拟变形链球菌和血链球菌的相互作用，因为它们在牙菌斑中的互斥是众所周知的。为了验证我们的假设，即种间相互作用会影响S. mutans和S. sanguinis之间的竞争结果，我们将：(a)开发基于唾液包被羟基磷灰石的双物种生物膜模型；(b)寻找与突变葡萄球菌和血葡萄球菌种间相互作用有关的新基因；(d)确定变形链球菌和血链球菌毒力基因相互影响的表达谱；(c)用原子力显微镜进一步描述变形葡萄球菌和血葡萄球菌之间的直接物理相互作用。相关性：将描述口腔生物膜中特定物种间竞争的毒力因素，有助于更好地理解和控制致龋齿变形链球菌的过度生长。

DESCRIPTION (provided by applicant): The Candidates background is in bacterial genetics, biofilm formation and bacterial virulence. The immediate goal is to prepare for a career as an independent scientist and to develop a model for bacterial interactions in the dental biofilm. The career objective is to become an independent scientist studying oral microbial ecology as ranked academic faculty. The mentored-phase will include the development of additional technical skills, topical, teaching and pedagogy, participation in the T32 MinnCResT program, and presenting in seminars and at conferences. The mentored phase will include establishment of interdisciplinary collaborations with researchers at UMN, which will be extended during the independent phase, when the main focus is the achievement of the proposed research. Environment: The proposed research will be performed at the School of Dentistry, UMN in the lab of Dr. M.C. Herzberg, a renowned expert in streptococcal biology especially in surface-adhesion proteins, biofilm development and the patho-physiology of S. sanguinis in endocarditis. Research: The role of S. mutans in the etiology of dental caries has been well investigated. S. mutans resides in the dental plaque with over 70 bacterial species. Indeed, interaction in the S. mutans-associated microbiome may determine the cariogenic potential of dental plaque. These interactions include modulation of gene expression, interspecies co-aggregation and growth inhibition. We hypothesize that oral streptococci compete in part by influencing virulence gene expression in the antagonized or challenged species by direct physical interactions and/or metabolic signaling. We will model interactions of S. mutans and S. sanguinis because their mutual exclusion in dental plaque is well-known. To test our hypothesis that interspecies interactions influence the outcome of the competition between S. mutans and S. sanguinis, we will: (a) Develop a dual-species biofilm model based on saliva coated hydroxyapatite; (b) Search for new genes involved in the interspecies interaction between S. mutans and S. sanguinis; (d) Determine the mutual influenced expression profile of S. mutans and S. sanguinis virulence genes; (c) Further characterize the direct physical interactions between S. mutans and S. sanguinis by atomic force microscopy. Relevance: Virulence factors will be characterized that specify inter-species competition in the oral biofilm, contributing to better understanding and control of the overgrowth of cariogenic S. mutans.