INTERACTION BETWEEN X NEMATOPHILUS AND ITS HOSTS

描述（改编自申请人摘要）：本提案旨在了解细菌如何与其真核宿主相互作用，以及营养物质的可用性如何影响这些相互作用。嗜线虫Xenorhabdus nematophilus提供了一个有价值的宿主微生物相互作用的模型系统：它是一种寄生在carpocapsae Steinernema线虫肠道中的共生体，也是一种杀死幼虫期昆虫的病原体。本研究的目的是确定嗜线虫线虫介导宿主相互作用的分子机制。许多革兰氏阴性菌的营养剥夺引发对压力的抵抗力增强和毒力决定因素的产生。这一反应部分受到特定的sigma因子ss的调控。本研究的第一个具体目的是分析ss及其依赖基因表达在嗜线虫线虫与其真核宿主的共生和致病性中的作用。这项工作的结果将开始解决嗜线虫线虫生存和适应的遗传调控，并将为养分的可用性如何影响宿主-细菌相互作用提供见解。嗜线虫线虫可能进化出多种调节机制，包括介导宿主相互作用的饥饿反应。虽然特异性Aim 1完全侧重于饥饿反应，但特异性Aim 2的目标是进行基因测试，以确定介导嗜线虫线虫和线虫之间共生的其他细菌调节机制。目标是获得并表征不再保留在线虫的肠囊泡内的嗜线虫X.突变体。这项工作将提供对共生至关重要的基因和基因产物的见解，并将有助于阐明嗜线虫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.