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CAREER: The Bioorganic Investigation of Species-Specific Biofilm Modulators

职业：物种特异性生物膜调节剂的生物有机研究

基本信息

批准号：
1755698
负责人：
William Wuest
金额：
$ 35.17万
依托单位：
Emory University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2020-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755698&HistoricalAwards=false
关键词：
CAREER Bioorganic Investigation Species Specific

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. William Wuest from Temple University to investigate the role species-specific natural products play in biofilm communities using an interdisciplinary approach comprised of synthetic, microbiological, and proteomic techniques. Bacterial communities are incredibly complex and dynamic. These communities, commonly referred to as biofilms, adversely impact both commercial interests and societal health. The inherent complexity of microbial biofilms and lack of scientific tools to interrogate these systems has limited both basic research and practical innovations. There is currently great interest in developing small molecules as chemicial biological tools to specifically alter such systems to aid in sorting out these processes. The proposed research will focus on naturally occurring materials that possess exquisite selectivity for one species of bacteria to better understand how they work. The multidisciplinary aspects of this program will allow graduate students and undergraduates to gain expertise in a broad range of modern research techniques. This project also integrates an outreach program to mentor inner-city Philadelphia elementary school students in preparation for the George Washington Carver Science Fair.Synthetic methods will be used to construct the natural products, analogs, and affinity probes for biological investigations and target identification. Affinity-based protein profiling will then be applied to determine the specific biological targets of these compounds providing insight into their mechanism of action. Concurrently, compounds will be tested both for their antimicrobial activity and their ability to specifically perturb bacterial biofilms. The identification of the mechanistic targets of these biofilm-modulating natural products seeks to increase our basic understanding of the biochemical processes of chemical signaling in bacterial biofilms.

凭借这一奖项，化学部门的生命过程化学项目资助了天普大学的William Wuest博士，利用跨学科的方法，包括合成、微生物和蛋白质组学技术，研究物种特异性天然产物在生物膜群落中的作用。细菌群落是非常复杂和动态的。这些群落通常被称为生物膜，对商业利益和社会健康都产生不利影响。微生物生物膜固有的复杂性和缺乏科学工具来询问这些系统限制了基础研究和实际创新。目前有很大的兴趣开发小分子作为化学生物工具，专门改变这些系统，以帮助整理这些过程。拟议的研究将集中在对一种细菌具有精细选择性的天然材料上，以更好地了解它们是如何工作的。该课程的多学科方面将使研究生和本科生获得广泛的现代研究技术方面的专业知识。该项目还整合了一个外展计划，指导费城市中心的小学生为乔治华盛顿卡弗科学博览会做准备。合成方法将用于构建天然产物、类似物和亲和探针，用于生物学研究和靶标鉴定。然后，基于亲和的蛋白质分析将被应用于确定这些化合物的特定生物学靶点，从而深入了解它们的作用机制。同时，将测试化合物的抗菌活性和它们特异性干扰细菌生物膜的能力。这些调节生物膜的天然产物的机制目标的鉴定旨在增加我们对细菌生物膜中化学信号的生化过程的基本理解。

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Target-Based Design of Promysalin Analogues Identifies a New Putative Binding Cleft in Succinate Dehydrogenase

DOI：
10.1021/acsinfecdis.0c00024
发表时间：
2020-06-12
期刊：
ACS INFECTIOUS DISEASES
影响因子：
5.3
作者：
Post, Savannah J.;Keohane, Colleen E.;Wuest, William M.
通讯作者：
Wuest, William M.

The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa

天然产物刺猬酮增强对铜绿假单胞菌的抗生素作用

DOI：
10.1002/anie.201903472
发表时间：
2019
期刊：
Angewandte Chemie International Edition
影响因子：
0
作者：
Zhao, Weining;Cross, Ashley R.;Crowe‐McAuliffe, Caillan;Weigert‐Munoz, Angela;Csatary, Erika E.;Solinski, Amy E.;Krysiak, Joanna;Goldberg, Joanna B.;Wilson, Daniel N.;Medina, Eva
通讯作者：
Medina, Eva

A Bisphenolic Honokiol Analog Outcompetes Oral Antimicrobial Agent Cetylpyridinium Chloride via a Membrane-Associated Mechanism