Interspecies Streptococcal Antagonisms in Oral Biofilms

描述(申请人提供)：应聘者背景为细菌遗传学、生物被膜形成和细菌毒性。目前的目标是为独立科学家的职业生涯做准备，并开发一个牙科生物膜中细菌相互作用的模型。职业目标是成为一名研究口腔微生物生态学的独立科学家，作为一名有等级的学术人员。指导阶段将包括发展额外的技术技能、专题、教学和教学方法，参与T32 MinnCResT计划，并在研讨会和会议上发表演讲。指导阶段将包括与UMN的研究人员建立跨学科合作，这种合作将在独立阶段扩大，届时主要重点是拟议研究的成果。环境：拟议的研究将在密歇根大学牙科学院的M.C.赫兹伯格博士的实验室进行，赫兹伯格博士是一位著名的链球菌生物学专家，尤其是在心内膜炎中的表面黏附蛋白、生物膜发育和血链球菌的病理生理方面。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。变形链球菌居住在牙菌斑中，有70多种细菌。事实上，变形链球菌相关微生物群中的相互作用可能决定牙菌斑的致龋性。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，口腔链球菌的竞争部分是通过直接的物理相互作用和/或代谢信号来影响被对抗或挑战的物种的毒力基因表达。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相互排斥是众所周知的。为了验证我们的假设，即物种间的相互作用影响变形链球菌和血链球菌之间的竞争结果，我们将：(A)建立基于唾液包裹的羟基磷灰石的双物种生物膜模型；(B)寻找参与变形链球菌和血链球菌物种间相互作用的新基因；(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)通过原子力显微镜进一步表征变形链球菌和血链球菌之间的直接物理相互作用。相关性：毒力因子的特征是指定口腔生物膜中物种间的竞争，有助于更好地理解和控制致龋性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.