Mechanisms underlying spatial interaction in the oral microbiota

摘要 人类口腔菌斑是一个多菌群落，其组成随健康和疾病的不同而变化。 最近的技术进步为人类的身份和丰富性提供了新的信息 在这些条件下的组成物种还不允许预测 特定的生物体。牙周上菌斑内可复制结构的生物地理学研究 以先进的显微镜方法为特征，表明关键生物体可能有助于 斑块结构。这些有序结构中的物种-物种相互接近暗示着 代谢物介导了它们之间的相互作用。我们的全球假设是，邻近物种处于健康状态 菌斑生物膜具有特定的代谢和物理相互作用，这些相互作用塑造了物理和 这个社区的组成结构。确定相邻设备之间的机械交互 物种，我们必须确定哪些物种在体内共存。初步数据显示， 存在高度丰富的Matruchotii棒杆菌和副流感嗜血杆菌 与几株链球菌直接相邻。这表明它们必须能够耐受pH和氧化 由口腔链球菌产生的压力。直接成像进一步表明，一些物种直接结合到 彼此或相互连接到宿主中间体，例如唾液蛋白。依附的物理手段 对马氏链球菌和副流感嗜血杆菌对链球菌属的影响。都是未知的。这项提议将 确定哪些链球菌与马氏葡萄球菌和副流感嗜血杆菌相互作用 显微镜(目标1)。它还将确定Matruchotii和H.parainfluenzae是否参与交叉 喂养与链球菌产生的代谢物的相互作用，并将确定以下机制 细菌通过转录组分析和突变体文库耐受pH和氧化应激 分析和定量代谢物测量(目标2)。最后，我们的提案将决定物理 细菌产生的因素，负责不同物种之间的粘连。这些遗嘱 通过对松材线虫和副流感嗜血杆菌的直接和随机诱变进行鉴定，并在 与已知的相互作用的链球菌种结合。这项提案的目标是确定 健康牙周上菌斑中相互作用的物种及其相互作用机制的研究 揭示了它们对斑块结构和组成的影响。我们的理由是我们 将确定促进健康斑块中高度丰富的生物之间相互作用的机制 并确定用于益生菌或预防性药物的候选物种及其相关相互作用 管理口腔菌斑社区以预防机会性感染的干预措施。

ABSTRACT Human oral plaque is a polymicrobial community whose composition varies during health and disease. Recent advances in technology have yielded new information on the identity and abundance of constituent species during these conditions yet do not allow predictions of direct interactions between specific organisms. The biogeography of reproducible structures within supragingival plaque has been characterized through advanced microscopy methods suggesting key organisms that may help arrange plaque structure. Species-species co-proximity within these ordered structures is suggestive of metabolite mediated interactions between them. Our global hypothesis is that adjacent species in healthy plaque biofilms have specific metabolic and physical interactions that shape both the physical and compositional structure of this community. To identify mechanistic interactions between adjacent species, we must determine which species exist together in vivo. Preliminary data indicates that the highly abundant Corynebacterium matruchotii and Haemophilus parainfluenzae bacterial species exist directly adjacent to several Streptococcus spp. suggesting they must be able to tolerate pH and oxidative stress produced by oral streptococci. Direct imaging further suggests that some species bind directly to each other or mutually to a host intermediate such as salivary protein. The physical means of attachment for C. matruchotii and H. parainfluenzae to Streptococcus spp. are unknown. This proposal will determine which Streptococcus species interact with C. matruchotii and H. parainfluenzae via microscopy (Aim 1). It will also determine if C. matruchotii and H. parainfluenzae participate in cross- feeding interactions with streptococcal produced metabolites and will identify mechanisms that either bacterium uses to tolerate pH and oxidative stress through transcriptome analyses, mutant library assays, and quantitative metabolite measurements (Aim 2). Lastly, our proposal will determine physical factors produced by bacteria that are responsible for co-adhesion between different species. These will be identified by direct and random mutagenesis of C. matruchotii and H. parainfluenzae and tested in combination with known interacting Streptococcus species. The goal of this proposal is to identify interacting species in healthy supragingival plaque and characterize mechanistic interactions between them, revealing how they may contribute to plaque structure and composition. Our rationale is that we will identify mechanisms that promote interactions between highly abundant organisms in healthy plaque and identify candidate species and their associated interactions for use in probiotic or prophylactic interventions to manage oral plaque communities to prevent opportunistic infection.