Root exudates as a new chemical-mining pool for isolation of novel antimicrobials

描述（由申请人提供）：医院感染的主要原因是革兰氏阳性菌肠球菌属。由于越来越多的不可治愈的，持续的E。faecalis和E.粪肠球菌感染后，立即出现了开发新的和替代疗法来对付粪肠球菌的热潮。faecalis和E.粪便感染这项探索性资助的目标是开发一种激进的方法来识别新型抗菌剂。我们以前的工作表明，植物可以作为一个简单和廉价的模式来表征E。粪便感染我们建议通过共培养大肠杆菌来筛选新型抗菌化合物。faecalis和E.与各种植物物种的粪便。该筛选将利用植物根部通过化合物的特异性激发来感知和响应细菌的能力，并且植物中的感染性将用作指示剂。未被细菌感染的植物可能会产生和分泌抗菌化合物。我们相信，该系统可以很容易地适用于与E。faecalis和E.屎室我们假设，自E. faecalis和E.屎肠球菌能够在实验室条件下感染植物，但一些没有被屎肠球菌感染的植物物种有可能感染屎肠球菌。faecalis和E.粪便分泌抗菌化合物。具体目标是：目的1：应用一种简单的根筛选方法检测E. faecalis和E.粪菌致病性鉴定抵抗E. faecalis和E.并收集其根系分泌物。在抗微生物测定中确定根分泌物的生物活性。目标二：鉴定和化学表征来自抗性和耐受性植物物种的根分泌物的化合物，其对E. faecalis和E.屎室预计这些新的努力将导致治疗大肠杆菌的新疗法的开发。faecalis和E.通过单独的药物或通过增强现有药物疗法的有效性来治疗粪便感染。公共卫生相关性：这项资助中概述的研究提出了一种治疗肠球菌感染的替代治疗方法的发展。预计这些新的努力将导致治疗E. faecalis和E.通过单独的药物或通过增强现有药物疗法的有效性来治疗粪便感染。

DESCRIPTION (provided by applicant): A leading cause of nosocomial infections is the Gram-positive bacteria Enterococcus species. Due to the increasing number of untreatable, persistent E. faecalis and E. faecium infections, there is an immediate surge to develop novel and alternate therapies dealing with E. faecalis and E. faecium infections. The goal of this exploratory grant is to develop a radical approach to identify novel classes of antimicrobials. Our previous work has demonstrated that plants could be used as a facile and inexpensive model to characterize E. faecalis infections. We are proposing the development of a screen for novel antimicrobial compounds by co-culturing E. faecalis and E. faecium with a variety of plant species. This screen would utilize the plant roots ability to sense and respond to the bacteria through specific elicitation of compounds and infectivity in plant would serve as an indicator. Plant not infected by the bacteria are likely producing and exuding antimicrobial compounds. We are confident that this system could easily be adapted for use with E. faecalis and E. faecium. We hypothesize that since E. faecalis and E. faecium is capable of infecting plants under laboratory conditions, there is an exciting possibility that some plant species that are not infected with E. faecalis and E. faecium exude antimicrobial compounds. The specific aims are Aim 1: To apply a simple root screening method to test E. faecalis and E. faecium pathogenicity. Identify plant species that resist infection by E. faecalis and E. faecium and collect their root exudates. Determine bioactivity of root exudates in antimicrobial assays. Aim 2: To identify and chemically characterize compound(s) from the root exudates of resistant and tolerant plant species that exhibit antimicrobial properties against E. faecalis and E. faecium. It is expected that these novel efforts will lead to the development of new therapeutics for treatment against E. faecalis and E. faecium infections either by a stand-alone drug or by enhancing the effectiveness of existing drug therapies. PUBLIC HEALTH RELEVANCE: The research outlined in this grant proposes the development of an alternative therapeutic approach to treat Enterococcus infections. It is expected that these novel efforts will lead to the development of new therapeutics for treatment of E. faecalis and E. faecium infections either by a stand-alone drug or by augmenting the effectiveness of existing drug therapies.