Elucidating the role of reactive nitrogen species in bacterial interactions

项目摘要/摘要 大多数细菌生活在复杂的多菌环境中，它们必须在那里竞争 营养、空间、氧气，并防御外源、宿主或细菌衍生的抗菌剂。 细菌群落的动态和行为会受到活性氮物种(RN)的很大影响， 它们是重要的信号分子、免疫介体和抗菌剂。不幸的是，有有限的 了解RNS如何调节多微生物群落的结构和功能及其影响 这种相互作用对宿主免疫力产生了影响，这在知识上造成了巨大的差距。之前的研究表明 探索RNS在微生物生理学中的作用主要使用单物种模型而不是 多微生物模型，更好地代表微生物的生活方式。我们的初步调查结果表明 共生细菌或有益细菌诱导RNS的产生以击败病原菌和 维持宿主体内的动态平衡。然而，目前还没有研究明确定义这种分子 控制共生细菌和RNS之间协同作用的机制，以及它们如何决定病原体- 东道主关系。在接下来的五年里，Mira申请中概述的研究将使用分子 遗传学、系统生物学工具(代谢组学、蛋白质组学和RNA测序)和果蝇 黑腹无脊椎动物模型确定RNS如何调节共生体和 病原体，并阐明这对宿主有什么影响。关键是RNS领域作为一个效应者 细菌种群动态的研究很少，但了解它是至关重要的，因为它有重要的健康意义。 后果。这项研究提案的发现将推动细菌-细菌相互作用领域的发展， 以及RNS应答在控制和调节宿主-病原体界面中的作用。我们的研究 可以潜在地提供有价值的机械数据，这些数据可以被利用来发展共生- 中介抗感染疗法。

Project Summary/Abstract Most bacteria are found living within complex polymicrobial environments where they must compete for nutrients, space, oxygen, and defend themselves against exogenous, host, or bacterial derived antimicrobials. Bacterial community dynamics and behavior can be greatly influenced by reactive nitrogen species (RNS), which are important signaling molecules, immune mediators, and antimicrobials. Unfortunately, there is limited understanding on how RNS regulate the structure and function of polymicrobial communities and what impact this interplay has on host immunity, which has created enormous gaps in knowledge. Previous studies that explore the role of RNS on microbial physiology predominantly use single species models instead of polymicrobial models, which better represent the lifestyle of microbes. Our preliminary findings indicate that commensal or beneficial bacteria induce the production of RNS to outcompete pathogenic bacteria and maintain homeostasis within a host. Yet, there are no studies that have clearly defined the molecular mechanisms that govern synergy between commensal bacteria and RNS, and how they dictate the pathogen- host relationship. Over the next five years, the studies outlined in this MIRA application will use molecular genetics, systems biology tools (metabolomics, proteomics, and RNA sequencing), and a Drosophila melanogaster invertebrate model to determine how RNS regulate interactions between commensals and pathogens and also elucidate what impact this has on the host. Critically the field of RNS as an effector of bacterial population dynamics is vastly understudied yet is vital to understand because it has significant health consequences. The findings of this research proposal will advance the field of bacterial-bacterial interactions, as well as the role of RNS responses in controlling and modulating the host-pathogen interface. Our studies could potentially provide valuable mechanistic data that can be harnessed for the development of commensal- mediated anti-infection therapies.