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细菌肠球菌。由于无法治愈的持续性粪肠杆菌和粪肠杆菌感染的数量不断增加，开发新的和替代疗法治疗粪肠杆菌和粪肠杆菌感染的需求立即激增。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素。我们之前的工作已经证明，植物可以作为表征粪肠球菌感染的简单而廉价的模型。我们建议通过将粪肠球菌和粪肠球菌与多种植物共培养来筛选新的抗菌化合物。该筛选将利用植物根系感知细菌的能力，并通过特定化合物的激发对细菌做出反应，植物的传染性将作为一个指标。未被细菌感染的植物可能会产生和散发抗菌化合物。我们相信，该系统可以很容易地适用于粪肠杆菌和粪肠杆菌。我们推测，由于粪肠球菌和粪肠球菌能够在实验室条件下感染植物，因此一些未被粪肠球菌和粪肠球菌感染的植物物种很可能会分泌出抗菌化合物。目的1：应用简单的根筛选法检测粪肠杆菌及其致病性。鉴定抗粪肠杆菌和粪肠杆菌感染的植物种类并收集其根分泌物。在抗菌试验中测定根分泌物的生物活性。目的2：从对粪肠杆菌和粪肠杆菌具有抗菌特性的抗性和耐受性植物物种的根分泌物中鉴定和化学表征化合物。预计这些新的努力将通过单独的药物或通过增强现有药物治疗的有效性，导致新的治疗方法的发展，以治疗粪肠球菌和粪肠球菌感染。公共卫生相关性：本拨款概述的研究建议开发一种治疗肠球菌感染的替代治疗方法。预计这些新的努力将导致通过单独药物或通过增强现有药物治疗的有效性来治疗粪肠球菌和粪肠球菌感染的新疗法的发展。

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.