Vibrio Virulence Determinants in a Benign Colonization

描述（由申请人提供）：人们越来越意识到天然微生物群在发展和维持健康方面所起的重要作用。这种认识使人们认识到了解人类和其他动物如何使有益细菌与其组织保持持久联系的重要性。有成千上万种这样的细菌与我们的皮肤、口腔、肠道和泌尿生殖系统的上皮表面有关，但我们对它们如何在我们的一生中与我们保持稳定的联系知之甚少。这些知识对于设计安全有效的治疗措施至关重要，因为我们必须在治疗疾病之前了解在宿主与其基本微生物伙伴之间建立稳定关系的因素。哺乳动物宿主-微生物相互作用的复杂性使他们的研究具有挑战性，并导致使用简化的模型关联，例如无细菌动物。另一种补充方法是使用自然动物模型，其中只有一种细菌与特定组织相关联，就像费氏弧菌与其宿主鱿鱼之间的共生关系一样。这些细菌与宿主的上皮表面结合数月，但最近的研究表明，这种共生体每天都会导致组织表面的消失，然后在几小时内恢复。这种破坏和恢复的自然循环为定义与细菌长期接触的上皮表面日常重塑的信号事件提供了极好的机会，并发现这种交流如何创造导致健康的动态稳定性。为了实现这一目标，我们建议通过以下方式来定义驱动细菌诱导的宿主上皮消失及其随后恢复的细胞、生化和遗传事件：(i)了解组织重塑日常周期背后的细胞事件，（ii）确定独特的共生体特征在上皮消失信号传导中的作用，以及（iii）确定在消失/恢复周期中起作用的保守的毒素样效应物。人们越来越认识到天然微生物群在发展和维持健康方面所起的重要作用。这种认识使人们认识到了解人类和其他动物如何使有益细菌与其组织保持持久联系的重要性。我们将研究一种天然的细菌关联，以确定共生体诱导的宿主组织日常重塑的基础信号事件，从而导致健康的持续相互作用。

DESCRIPTION (provided by applicant): There is a growing awareness of the essential role that the natural microbiota play in the development and maintenance of health. This awareness has led to recognition of the importance of understanding how humans and other animals maintain beneficial bacteria in persistent associations with their tissues. There are thousands of such bacterial species associated with the epithelial surfaces of our skin, mouths, gut tracts and urogenital systems, yet we know very little about how they maintain a stable association with us throughout our lives. This knowledge is vital to designing safe and effective therapeutic measures against pathogens, as we must understand the factors that create stabile relationships between hosts and their essential microbial partners before we treat disease. The complexity of mammalian host-microbe interactions has made their study challenging, and has led to the use of simplified model associations such as gnotobiotic (germ-free) animals. Another, complementing, approach has been the use of natural animal models in which only a single bacterium is associated with a specific tissue, as in the symbiosis between Vibrio fischeri and its host squid. These bacteria associate for months with the epithelial surfaces of the host, but recent work has revealed that the symbionts induce a daily effacement of the tissue's surface, which then recovers within hours. This natural cycle of disruption and recovery provides an excellent opportunity to define the signaling events underlying the daily remodeling of an epithelial surface in long-term contact with its bacteria, and discover how this communication creates a dynamic stability that leads to health. To reach this goal we propose to define the cellular, biochemical and genetic events that drive the bacteria-induced effacement of the host epithelium, and its subsequent recovery, by: (i) understanding the cellular events underlying the daily cycle of tissue remodeling, (ii) determining the role of unique symbiont characters in signaling epithelial effacement, and (iii) identifying conserved toxin-like effectors that act in the effacement/recovery cycle PUBLIC HEALTH RELEVANCE: There is a growing awareness of the essential role that the natural microbiota play in the development and maintenance of health. This awareness has led to a recognition of the importance of understanding how humans and other animals maintain beneficial bacteria in persistent associations with their tissues. We will investigate a natural bacterial association to define the signaling events that underlie a symbiont-induced daily remodeling of the host's tissues that leads to a healthy persistent interaction.