Elucidating the role of reactive nitrogen species in bacterial interactions

项目概要/摘要 大多数细菌被发现生活在复杂的多微生物环境中，在那里它们必须竞争 营养素、空间、氧气，并保护自己免受外源性、宿主或细菌衍生的抗菌剂的侵害。 活性氮（RNS）对细菌群落动态和行为有很大影响， 它们是重要的信号分子、免疫介质和抗微生物剂。不幸的是， 了解RNS如何调节多微生物群落的结构和功能，以及对 这种相互作用对宿主免疫力产生了影响，造成了巨大的知识空白。之前的研究 探索RNS对微生物生理学的作用主要使用单种模型，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， 益生菌或有益菌诱导RNS的产生以胜过致病菌， 维持宿主体内的稳态。然而，还没有研究清楚地定义了 控制肠道细菌和RNS之间协同作用的机制，以及它们如何决定病原体- 宿主关系在接下来的五年里，这项MIRA申请中概述的研究将使用分子生物学技术， 遗传学，系统生物学工具（代谢组学，蛋白质组学和RNA测序），以及果蝇 黑腹无脊椎动物模型，以确定RNS如何调节之间的相互作用， 病原体，并阐明这对宿主的影响。关键是，RNS作为一种效应物， 细菌种群动力学的研究还远远不够，但了解它是至关重要的，因为它具有重要的健康意义。 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反应在控制和调节宿主-病原体界面中的作用。我们的研究 可能会提供有价值的机械数据，可以利用这些数据来发展生物技术， 介导的抗感染疗法。

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.