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Genetic Analysis of Beneficial Bacterial Colonization

有益细菌定植的遗传分析

基本信息

批准号：
10384521
负责人：
Mark J Mandel
金额：
$ 21.96万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2022-05-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY FOR PARENT GRANT R01GM119627 The objective of my laboratory is to characterize how molecular communication between bacteria and their animal hosts leads to specific and reproducible colonization. To accomplish this goal, the laboratory studies the V. fischeri-squid system. This system is advantageous because bacteria colonize through the natural route of infection, all animals are colonized within three hours of bacterial inoculation into the seawater, the bacteria can be subject to detailed genetic manipulation, and the precise site of infection can be imaged directly in the live animal host, allowing for cutting edge genetic and genomic approaches. Focusing on how squid are reproducibly colonized by the specific symbiont, to the exclusion of the millions of competing bacteria in seawater, has revealed key roles for bacterial aggregation and biofilm formation in promoting specific host- microbe interactions. Recently our global genetic screen to identify colonization factors revealed multiple novel biofilm activators and identified an orphan histidine kinase, which acts as a negative regulator of Syp biofilm development in vivo. To elucidate the pathways governing colonization and biofilm development in the animal host we will (1) dissect the molecular details of the novel histidine kinase pathway, (2) define at high temporal and spatial resolution the steps necessary for the establishment of this mutualistic relationship, and (3) characterize the role of new colonization factors using genetic and metabolomic approaches. Since the strategies used by V. fischeri to interact with its host are conserved in other host-microbe systems, our findings will be applicable to understand other beneficial associations as well as interactions between pathogenic bacteria and their hosts.

家长资助项目摘要R01GM119627 我的实验室的目标是描述细菌和它们之间的分子通讯动物寄主导致了特定的和可复制的殖民。为了实现这一目标，实验室研究了五、鱼-鱿鱼系统。这个系统是有利的，因为细菌通过自然途径定植感染后，所有动物都会在3小时内将细菌接种到海水中，这种细菌可以接受详细的基因操作，感染的准确位置可以直接在活体动物宿主，允许尖端的遗传和基因组方法。关注鱿鱼是怎么回事被特定的共生体繁殖，从而排除了数百万竞争的细菌海水，揭示了细菌聚集和生物膜形成在促进特定宿主- 微生物相互作用。最近，我们的全球基因筛查发现了多个新的殖民因素生物膜激活剂，并鉴定了一种孤儿组氨酸激酶，它作为SYP生物膜的负调节因子体内发育。阐明动物体内定植和生物膜发育的途径我们将(1)剖析新的组氨酸激酶途径的分子细节，(2)在高时间定义和空间分辨率为建立这种互惠关系所必需的步骤，以及(3) 利用遗传学和代谢学方法表征新的殖民因素的作用。自.以来费氏弧菌与宿主相互作用的策略在其他宿主-微生物系统中是保守的，我们的发现将适用于理解其他有益的联系以及致病因子之间的相互作用细菌和它们的宿主。