Oxidative and Nitrosative Stress in Burkholderia

该项目的目标是确定适应性反应的主要分子组成部分 类鼻疽伯克霍尔德氏菌活性氧和氮胁迫。B。假鼻疽是病原体 类鼻疽高死亡率，困难的治疗方案，和广泛的可用性致病 菌株导致了B的分类。假鼻疽作为潜在的生物恐怖分子更有效 需要治疗和有效的疫苗来防御B。假性鼻疽发作。期间 在感染过程中，细胞内病原体必须科普各种宿主介导的应激条件， 特别是吞噬细胞的抗菌特性。B。假鼻疽侵入并持续存在于 巨噬细胞大环内酯产生抗微生物活性氧和氮物质（ROS和RNS）。 细胞内病原体避免这些抗菌剂的机制是它们生存的核心 在感染期间。存在于B中的与ROS抗性有关的基因。类鼻疽基因组 包括oxyR和soxR基因，以及超氧化物歧化酶、过氧化氢酶和烷基化酶的基因。 氢过氧化物还原酶。我们的工作假设是：1）机制，使B。假鼻疽 抵抗ROS和RNS的杀伤对于疾病期间的存活至关重要，因此是 抗微生物干预和2）耐药蛋白在疾病期间高度表达，因此是理想的 疫苗开发的候选人。我们将学习B。假鼻疽对氧化和亚硝化的适应 压力使用我们结核分枝杆菌研究中完善的全局表达谱方法。我们 将识别B的转录应答。假鼻疽对ROS和RNS的作用，决定了主要的 氧化应激调节因子（OxyR和SoxR）在防御ROS和RNS中的作用，并确定关键抗性 用于疫苗和药物开发的蛋白质。项目交互除了 与其他项目成员（例如Vasil博士，Holmes博士和Vazquez-Torres博士）一起提出这一建议，我们将与 博士Slayden（基因组学/蛋白质组学核心-CSU）在微阵列技术的开发和使用中， 治疗剂的潜在靶蛋白的评价，罗宾逊博士（Select Agent Archive-BYU） 以接触代表B。假鼻疽分离株，和施韦泽博士（微生物遗传学-CSU）在条款 B的遗传学假鼻疽

Introduction The goal of this project is to identify the major molecular components of the adaptive response of Burkholderia pseudomalleiio reactive oxygen and nitrogen stress. B. pseudomallei is the causative agent of melioidosis. High mortality rates, difficult treatment regimens, and the wide availability of pathogenic strains have led to the classification of B. pseudomallei as a potential bioterrorism agent. More effective treatments and an efficacious vaccine are needed to defend against a B. pseudomallei attack. During the course of infection, intracellular pathogens must cope with a variety of host-mediated stress conditions, in particular, the antibacterial properties of phagocytic cells. B. pseudomallei invades and persists in macrophages. Macrophages produce antimicrobial reactive oxygen and nitrogen species (ROS and RNS). Mechanisms by which intracellular pathogens avoid these antibacterial agents are central to their survival during infection. Genes involved in resistance to ROS that are present in the B. pseudomallei genome include the oxyR and soxR genes, and the genes for superoxide dismutases, catalases, and alkyl hydroperoxide reductases. Our working hypotheses are: 1) mechanisms which allow B. pseudomallei to resist killing by ROS and RNS are critical for survival during disease and are thus logical candidates for antimicrobial intervention and 2) resistance proteins are highly expressed during disease and thus ideal candidates for vaccine development. We will study B. pseudomallei's adaptation to oxidative and nitrosative stress using global expression profiling methods refined in our studies of Mycobacterium tuberculosis. We will identify the transcriptional response of B. pseudomallei to ROS and RNS, determine the role of the major oxidative stress regulators (OxyR and SoxR) in defense against ROS and RNS, and identify key resistance proteins for vaccine and drug development. Project interactions In addition to the interactions described in this proposal with other project members (e.g. Drs. Vasil, Holmes, & Vazquez-Torres), we will interact with Dr. Slayden (Genomics/Proteomics Core-CSU) in the development and use of microarray technology and the evaluation of potential target proteins for therapeutic agents, Dr. Robinson (Select Agent Archive-BYU) for access to representative B. pseudomallei isolates, and Dr. Schweizer (Microbial Genetics-CSU) in terms of genetics of B. pseudomallei.