REQUIREMENTS FOR BACTERIAL COLONIZATION OF ANIMAL TISSUE

在共生（互惠）和发病机制之间有一条细微的界限。大多数动物（如果不是全部的话）都被细菌占据，其中许多细菌--有机体的“正常植物群”--是被容忍甚至鼓励的。为了与动物建立共生关系，原核生物必须能够识别并响应特定的环境，与宿主建立沟通，在宿主组织中定殖，逃避防御机制，坚持和繁殖。这些步骤中的每一个都反映在病原体的相互作用中，无论是原发性的还是机会性的，即使是正常的植物群，如果过度繁殖或引入它们通常不栖息的区域，也有致病的潜力。尽管细菌-动物共生体无处不在，但人们对这些相互作用的遗传和分子细节知之甚少。除了增加对这些重要的原核生物-真核生物联盟的基本理解外，共生相互作用的研究有望提高对病原生物如何采用、破坏或绕过导致共生的机制以及它们为何引起真核细胞不同反应的理解。生物发光海洋细菌费氏弧菌（Vibrio fischeri）与其宿主鱿鱼Euprymna scolopes之间的共生关系为研究可以与动物宿主形成长期互利关系的细菌的生物学提供了绝佳的机会。共生关系在生物体水平上得到了很好的表征。我们现在建议开始这些生物体之间的相互作用的详细分子表征，包括建立共生状态，两个生物体之间的信号和发展变化发生在双方的合作伙伴的共生进展。拟议的研究将调查V fischeri殖民宿主组织的要求，使用一个简单的屏幕转座子插入突变体缺陷的初始共生事件。鉴定和表征的关键定植基因将奠定基础，了解信号交换的原核生物和真核生物之间建立一个长期的协会。

There is a fine line between symbiosis (mutualism) and pathogenesis. Most, if not all, animals are colonized by bacteria, many of which-the organism's "normal flora"-are tolerated or even encouraged. To establish a symbiotic relationship with an animal, a prokaryotic organism must be able to recognize and respond to a specific environment, establish communication with the host, colonize the host tissue, evade defense mechanisms, persist and multiply. Each of these steps is mirrored in pathogenic interactions, whether primary or opportunistic-and even normal flora have pathogenic potential in the event of excessive multiplication or introduction into areas they do not ordinarily inhabit. Despite the ubiquity of bacterium-animal symbioses, little is known about the genetic and molecular details of these interactions. In addition to increasing basic understanding of these important prokaryote-eukaryote alliances, the study of symbiotic interactions is expected to improve understanding of how pathogenic organisms adopt, subvert, or bypass the mechanisms leading to symbiosis and why they provoke dissimilar responses from the eukaryotic cell. The symbiosis between the bioluminescent marine bacterium Vibrio fischeri and its host, the squid Euprymna scolopes, provides an excellent opportunity to study the biology of a bacterium which can form a long- term, mutualistic association with an animal host. The symbiosis has been well-characterized at the organismal level. We now propose to begin the detailed molecular characterization of the interactions between these organisms, including establishment of the symbiotic state, signalling between the two organisms and developmental changes occurring in both partners as the symbiosis progresses. The proposed research will investigate the requirements for V fischeri colonization of host tissue, using a straightforward screen for transposon-insertion mutants defective in the initial symbiotic events. Identification and characterization of the critical colonization genes will lay the foundation for understanding signal exchange between a prokaryote and a eukaryote during the establishment of a long-term association.