Studying the Protective Effects of Normal Oral Flora

摘要： 目前大多数微生物发病机制的研究都集中在了解不同的毒力因子如何 使病原体能够干扰和入侵正常的菌群。这项研究的重点是“故事的另一面”： 如何将正常的菌群作为预防和抵御外来病原体入侵的第一道防线。 了解寄主植物抵抗外来入侵的机制 细菌，包括病原体，具有重要的科学和临床意义，这是这次会议的主要目标。 申请。 在我们的初步研究中，我们建立了一个研究群落水平的体外模型系统 利用口腔和肠道微生物抵抗不同来源细菌的侵袭 由老鼠衍生的社区。具体地说，我们确定了一个独特的微生物联盟，由三个 小鼠口腔微生物区系中参与限制肠道入侵的独特细菌物种- 衍生的大肠埃希菌。进一步的研究表明，这三个物种形成了一个独特的社会结构；他们 分别扮演传感器、调解人和杀手的角色，并在预防 大肠杆菌与口腔微生物群落的整合。我们的数据暗示了复杂的信号事件 该财团受到了入侵物种的挑战。最耐人寻味的是，我们展示了类似的 人类口腔微生物群落中也存在抗侵袭现象。基于这些 发现，我们假设本土微生物群对外来细菌的入侵抵抗力 是一个高度协调的社区级功能，它涉及到广泛的分子事件 承认外来入侵者、物种间交流和管制杀戮生产 分子。了解这些分子事件将提供有价值的见解，以保护 由正常的植物群赋予的效果。 我们认识到这样一个事实，即小鼠微生物区系研究将成为研究 详细的分子机制以及为未来的动物研究奠定基础，而人类 微生物区系研究对于确定观察到的侵袭性耐药性的临床相关性至关重要。 机制，因此，该应用程序研究了这两个系统中的这一有趣现象。两大主打 这项应用的目标是：1)进一步了解分子机制的抗入侵利用 建立完善的从小鼠口腔菌群中衍生的三物种联合体模型系统；2)解决 通过将研究扩大到人类口腔微生物区系，观察到的保护机制的临床相关性。 这些研究的结果将为正常的植物群如何抵抗提供有洞察力的机制信息。 外来病原体在分子水平上的入侵。这些关键信息可能会直接导致小说 寻求加强对正常菌群的保护作用的治疗方法。

Abstract: Most current microbial pathogenesis studies are focused on understanding how different virulence factors may enable pathogens to disturb and invade the normal flora. This study focuses on “the other side of the story”: how normal flora may prevent and resist the invasion of foreign pathogens as the first line of defense. Understanding the mechanisms underlying the invasion resistance of host flora against foreign invading bacteria, including pathogens, is of great scientific and clinical importance, which is the main goal of this application. During our preliminary studies, we established an in vitro model system for studying the community-level invasion resistance against the colonization of bacteria of different origin, using oral and gut microbial communities derived from mice. Specifically, we identified a unique microbial consortium composed of three distinct bacterial species within murine oral microbial flora that were involved in restricting invasion of gut- derived Escherichia coli. Further studies revealed that these three species form a unique social structure; they act as the sensor, the mediator and the killer, respectively, and have coordinated roles in preventing the integration of E. coli into oral microbial communities. Our data implicated sophisticated signaling events when the consortium was challenged with the invading species. Most intriguingly, we demonstrated that a similar invasion resistance phenomenon exists in the human oral microbial community as well. Based on these findings, we hypothesize that indigenous microbiota-based invasion resistance against foreign bacteria is a highly coordinated community-level function, which involves extensive molecular events for recognition of foreign invaders, inter-species communication and regulated production of killing molecules. Understanding these molecular events will provide valuable insights into the protective effect conferred by normal flora. We recognize the fact that a murine microbiota study will serve as an ideal model system for investigating the detailed molecular mechanisms as well as laying a foundation for future animal studies, and that a human microbiota study is critical for determining the clinical relevance of the observed invasion resistance mechanism, therefore, this application investigates this intriguing phenomenon in both systems. The two main goals of this application are: 1) To further understand the molecular mechanism of invasion resistance using the well established three-species consortium model system derived from murine oral flora; 2) To address the clinical relevance of the observed protective mechanism by expanding the study to human oral microbiota. The results of these studies will provide insightful mechanistic information on how the normal flora may resist the invasion of foreign pathogens at the molecular level. This critical information could lead directly to novel therapeutic approaches that seek to enhance the protective efforts of normal flora.