Identification of novel secondary metabolites produced by symbiotic Proteobacte

CETR的这一科学计划致力于发现和开发细菌产生的分子，这些分子可以成为治疗剂，提供新的抗真菌和抗细菌剂，以应对耐药微生物病原体对人类健康构成的日益严峻的挑战。对细菌产生的分子的强调部分是历史性的-我们大多数有用的抗真菌剂和抗细菌剂都是，或来自细菌产生的分子-部分是生态性的-正在研究的细菌是高等生物体的共生体，并且是已知的，或可能是抗菌剂的生产者。这一总体目标基于三个具体目标：具体目标1：探索共生环境生态位和分类群，以生产对耐药目标真菌和细菌具有抗菌活性的新型化合物。该项目将主要集中在已从共生环境中分离的变形菌。将通过16 S测序测量的系统发育新奇对菌株进行优先排序。具体目标二：开发可靠的方法来鉴定对耐药目标真菌和细菌具有抗菌活性的新型天然产物。将通过培养、共培养、基因组测序、诱导子和异源表达等技术检查选定菌株的生物合成潜力。具体目标3：确定共生环境，分类群和生物测定的组合，最有效地发现安全和有效的铅抗菌剂。将进一步检查筛选核心中具有高活性水平的化合物。将优化生产，制备半合成衍生物，并开始努力确定作用机制。

This Scientific Program in the proposed CETR addresses the discovery and development of bacterially produced molecules that could become therapeutic agents to provide new antifungal and antibacterial agents to address the growing challenge to human health posed by resistant microbial pathogens. The emphasis on bacterially produced molecules is partly historical - most of our useful antifungal and antibacterial agents are, or were derived from, bacterially produced molecules - and partly ecological - the bacteria being investigated are symbionts on higher organisms and are known, or likely, producers of antimicrobials. This overall goal is based on three specific aims: Specific Aim 1: Explore symbiotic environmental niches and taxa for the production of novel compounds with antimicrobial activity against drug resistant target fungi and bacteria. This project will focus largely on Proteobacteria that have been isolated from symbiotic environments. Strains will be prioritized by phylogenetic novelty as measured by 16S sequencing. Specific Aim 2: Develop robust methods to identify novel natural products with antimicrobial activity against drug resistant target fungi and bacteria. Selected strains will be examined for biosynthetic potential through techniques such as culturing, co-culturing, genome sequencing, elicitors, and heterologous expression. Specific Aim 3: Identify combinations of symbiotic environments, taxa, and biological assays that most efficiently discovery safe and effective lead antimicrobials. Compounds with high activity levels in the screening cores, will be further examined. Production will be optimized, semi-synthetic derivatives will be prepared, and efforts to identify mechanism of action begun.