Vibrio Virulence Determinants in a Benign Colonization

描述(由申请人提供)：越来越多的人意识到自然微生物区系在健康发展和维护中所起的重要作用。这种认识使人们认识到了解人类和其他动物如何保持有益细菌与其组织持续联系的重要性。有成千上万种这样的细菌与我们皮肤、口腔、肠道和泌尿生殖系统的上皮表面相关，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。这一知识对于设计针对病原体的安全有效的治疗措施至关重要，因为在我们治疗疾病之前，我们必须了解在宿主及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，如GnotoBiotic(无菌)动物。另一种补充方法是使用自然动物模型，在自然动物模型中，只有一种细菌与特定组织相关，就像鱼弧菌与其宿主鱿鱼之间的共生一样。这些细菌与宿主的上皮表面联系了几个月，但最近的研究表明，共生体每天会导致组织表面的消失，然后在几个小时内恢复。这种破坏和恢复的自然循环提供了一个极好的机会，可以定义长期与细菌接触的上皮表面每日重塑背后的信号事件，并发现这种沟通如何创造一种动态稳定，从而导致健康。为了达到这一目标，我们建议通过以下方式定义驱动细菌诱导的宿主上皮丧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中潜在的细胞事件，(Ii)确定独特的共生体特征在信号上皮丧失中的作用，以及(Iii)确定在消除/恢复周期中起作用的保守的毒素样效应因子与公共卫生的相关性：人们越来越意识到自然微生物区系在健康的发展和维持中发挥的重要作用。这种认识使人们认识到了解人类和其他动物如何保持有益细菌与其组织持续联系的重要性。我们将研究一种自然的细菌联系，以定义信号事件，这些事件是共生菌诱导的宿主组织日常重塑的基础，从而导致健康的持久相互作用。

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.