Molecular mechanisms of X. nematophila-nematode interaction

描述（由申请人提供）：我们研究的长期目标是阐明介导宿主-微生物相互作用的分子机制，并了解微生物过程如何影响这些关系的结果。我们用于这些研究的模式细菌是嗜线虫杆菌，它既是（线虫的）互利者，也是（昆虫的）病原体，因此是理解这两种关系的极好模型。该建议着重于X之间的互惠关系。同时也补充了我们实验室在X染色体上单独资助的工作。嗜热菌致病机理。研究X的互惠互动。嗜线虫及其线虫宿主将扩大我们对动物如何进化以及与其微生物区系保持特定和依赖关系的理解。这项建议的具体目标是面向遗传和生化表征我们已经确定的几个殖民启动因素，以及它们之间的相互作用。 具体目标1将测试我们的假设，即膜定位的定植因子的功能，坚持线虫细胞，金属运输，和/或信号转导。这些研究的结果将阐明Nil（线虫肠道定位）蛋白在定殖事件中的作用，阐明革兰氏阴性病原体的Nil同源物在启动感染中的可能功能，并进一步了解介导宿主范围特异性的分子机制。 具体目标2旨在剖析定植所需的两个调节因子的功能，一个sigma因子和一个调节RNA。这些实验将有助于深入了解X感知到的信号。在定殖过程中的嗜水气单胞菌，进一步定义了定殖特异性调节子，并扩大了我们的知识的作用，一个普遍存在的转录因子在自然生态的细菌。

DESCRIPTION (provided by the applicant): The long-term goal of our research is to elucidate molecular mechanisms mediating host-microbe interactions and to learn how microbial processes affect the outcome of these relationships. The model bacterium we use for these studies is Xenorhabdus nematophila, which is both a mutualist (of nematodes) and a pathogen (of insects), and therefore an excellent model to understand both types of relationships. This proposal focuses on the mutualism between X. nematophila and the nematode and complements separately funded work in our lab on X. nematophila pathogenesis. Examining the mutualistic interactions of X. nematophila and its nematode host will expand our understanding of how animals evolve and maintain specific and dependent relationships with their micro-flora. The specific aims of this proposal are geared toward genetically and biochemically characterizing several of the colonization initiation factors we have identified, as well as their interactions with each other. Specific Aim 1 will test our hypotheses that membrane-localized colonization factors function in adherence to nematode cells, metal transport, and/or signal transduction. The results of these studies will elucidate the roles of Nil (nematode intestine localization) proteins in colonization events, shed light on the possible functions of Nil homologs of gram-negative pathogens in initiating infections, and further our understanding of molecular mechanisms mediating host-range specificity. Specific Aim 2 is designed to dissect the functions of two regulators required for colonization, a sigma factor and a regulatory RNA. These experiments will yield insight into the signals perceived by X. nematophila during colonization, further define a colonization-specific regulon, and expand our knowledge of the role of a ubiquitous transcription factor in the natural ecology of a bacterium.