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

描述(申请人提供)：医院感染的一个主要原因是革兰氏阳性细菌肠球菌。由于无法治疗的持续性粪肠球菌和粪肠球菌感染的数量不断增加，立即出现了开发治疗粪肠球菌和粪肠球菌感染的新的和替代疗法的热潮。这项探索性拨款的目标是开发一种激进的方法来识别新型抗菌剂。我们以前的工作已经证明，植物可以作为一种简便和廉价的模型来表征粪肠球菌感染的特征。我们建议开发一种筛选新型抗菌化合物的方法，通过将粪肠球菌和粪肠球菌与各种植物物种进行共培养。这种筛选将利用植物的根通过特定的化合物诱导来感知和响应细菌的能力，植物的感染性将作为一个指标。没有被细菌感染的植物很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应粪肠球菌和粪肠球菌的使用。我们推测，由于粪肠球菌和粪肠球菌能够在实验室条件下侵染植物，所以一些没有感染粪肠球菌和屎肠杆菌的植物物种很有可能会分泌抗菌化合物。其具体目的是：1.应用一种简便的根部筛选方法检测粪肠球菌和粪肠球菌的致病性。鉴定抵抗粪肠球菌和粪肠球菌感染的植物种类，并收集它们的根分泌物。根分泌物的抗菌活性测定。目的：从抗性和耐受性植物的根分泌物中鉴定出对粪肠球菌和粪肠球菌具有抗菌活性的化合物(S)，并对其进行化学表征。预计这些新的努力将导致开发新的疗法，通过单独的药物或通过加强现有药物疗法的有效性来治疗粪肠球菌和粪肠球菌感染。公共卫生相关性：这项赠款中概述的研究建议开发一种替代治疗方法来治疗肠球菌感染。预计这些新的努力将导致开发新的疗法来治疗粪肠球菌和粪肠球菌感染，无论是通过单独的药物还是通过加强现有药物疗法的有效性。

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.