INTERACTION BETWEEN X NEMATOPHILUS AND ITS HOSTS

描述(改编自申请人的摘要)：这项建议旨在了解细菌如何与它们的真核宿主相互作用，以及营养的可用性如何影响这些相互作用。嗜线虫杆菌为寄主微生物相互作用提供了一个有价值的模式系统：它是一种寄生在肉质斯氏线虫肠道中的共生菌，也是一种杀死幼虫阶段昆虫的病原体。本研究的目的是确定嗜线虫调节宿主相互作用的分子机制。在许多革兰氏阴性菌中，营养缺乏会引发对压力的抵抗力增强，并产生毒力决定因素。这种反应部分地受特定的西格玛因子ss调节。这一建议的第一个具体目的是分析ss和ss依赖的基因表达在嗜线虫与其真核宿主共生和致病中的作用。这项工作的结果将开始解决线虫生存和适应的遗传调控，并将为深入了解营养物质的可用性如何影响宿主与细菌的相互作用提供洞察。嗜线虫可能进化出多种调节机制，包括调节宿主相互作用的饥饿反应。虽然特定目标1完全集中在饥饿反应上，但特定目标2的目标是进行基因测试，以确定介导嗜线虫和线虫共生的额外细菌调节机制。其目标是获得和鉴定不再保留在线虫肠道小泡内的嗜线虫突变体。这项工作将提供对共生必不可少的基因和基因产物的洞察，并将有助于阐明嗜线虫和其他细菌中宿主相互作用的调节。

DESCRIPTION (Adapted from the Applicant's Abstract): This proposal is aimed at understanding how bacteria interact with their eukaryotic hosts and how the availability of nutrients affects these interactions. The bacterium Xenorhabdus nematophilus provides a valuable model system of host microbe interactions: it is a symbiont that resides in the intestine of the nematode Steinernema carpocapsae and a pathogen that kills larval stage insects. The goals of this research are to identify the molecular mechanisms used by X. nematophilus to mediate host interactions. Nutrient deprivation in many Gram-negative bacteria triggers development of increased resistance to stress and the production of virulence determinants. This response is partially regulated by a specific sigma factor, ss. The first specific aim of this proposal is to analyze the role of ss and ss-dependent gene expression in the symbiosis and pathogenicity of X. nematophilus with its eukaryotic hosts. The results of this work will begin to address the genetic regulation of survival and adaptation in X. nematophilus and will provide insight into how the availability of nutrients affects host-bacterium interactions. X. nematophilus is likely to have evolved multiple regulatory mechanisms, including the starvation response, that mediate host interactions. While specific Aim 1 focuses entirely on the starvation response, the goal of Specific Aim 2 is to perform genetic tests to identify additional bacterial regulatory mechanisms that mediate symbiosis between X. nematophilus and the nematode. The goal is to obtain and characterize X. nematophilus mutants that are no longer retained within the intestinal vesicles of nematodes. This work will provide insight into the genes and gene products that are essential for symbiosis and will aid in the elucidation of the regulation of host interactions in X. nematophilus and other bacteria.