Antibiotic discovery from environmental microorganisms of Brazil

从巴西环境微生物中发现抗生素

基本信息

批准号：
10316219
负责人：
Kim Lewis
金额：
$ 15.7万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-16 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10316219
关键词：
Acinetobacter baumannii Animals Antibiotics Antimicrobial Resistance Bacteremia Bacteria Binding Biodiversity Brazil Cell Wall Collection Development Diffusion Drug resistance Environment Escherichia coli Eukaryota Goals Gram-Negative Bacteria Gram-Positive Bacteria High Pressure Liquid Chromatography Infection Klebsiella pneumoniae Label Lead Location Membrane Proteins Methods Mining Mus Mycobacterium tuberculosis Natural Products Natural Products Chemistry Nature New England Peptide Hydrolases Peptidoglycan Planets Plants Probability Problem Solving Pseudomonas aeruginosa Rain Recovery Resistance Resistance development Resources Ribosomal DNA Sampling Scientist Septicemia Soil Source Staphylococcus aureus Structure Teichoic Acids Thigh structure Universities Work World Health Organization Writing antimicrobial base combat cytotoxicity drug discovery experience forest methicillin resistant Staphylococcus aureus microbial microorganism novel novel antibiotic class pathogen prevent resistance frequency screening soil sampling

项目摘要

Abstract We are currently experience a crisis of antimicrobial resistance, and the World Health Organization identified the need to combat drug resistant Gram negative pathogens as “critical”. The last class of compounds acting against Gram negative bacteria was introduced over 50 years ago. The most effective strategy to prevent antimicrobial resistance is by introducing novel compounds that act against AMR pathogens and have low probability of resistance development. We recently identified a novel antimicrobial, teixobactin, that shows no detectable resistance against Gram positive bacteria (Ling et al., Nature 2015). Teixobactin is currently in IND-enabling development against important Gram positive AMR infections such as MRSA bacteremia. We more recently discovered another natural product antibiotic, darobactin, with unusually low resistance development that acts against Gram negative AMR pathogens. While these are encouraging advances, a considerable effort is spent on rediscovery of the same producing species and compounds. We reason that mining the rich diversity of Brazilian soils with our approaches will provide access to novel antibiotic to combat the AMR crisis. The Brazilian rain forest has the highest diversity of plants and animals, and we expect the same to be true for microorganisms. Indeed, microorganism directly or loosely associate with eukaryotes, and degrade their products. The goal of this project is to evaluate soils from Brazil for their microbial diversity, to screen isolates for compounds with Gram negative activity, and to isolate and validate novel antimicrobials. If we are able to find novel antimicrobials from soils of New England, it is reasonable to expect that the pace of discovery will increase once we access an environment with the richest diversity on the planet. This project brings together Dr. Kim Lewis, Northeastern University, an expert in drug resistance and drug discovery, and Dr. Monica Pupo, University Sao Paulo, an expert in natural products chemistry. These scientists collaborated on writing the proposal and will work closely together on its execution.

抽象的我们目前正在遇到抗菌素抵抗的危机，世界卫生组织确定了需要将耐药的革兰氏阴性病原体与“关键”作斗争。最后一类反对的化合物革兰氏阴性细菌是在50年前引入的。预防抗菌抗性的最有效策略是引入新颖的化合物对AMR病原体作用，并且耐药性发展的可能性较低。我们最近确定了一本小说抗菌，静远非洲分泌蛋白，显示出对革兰氏阳性细菌的可检测性抗性（Ling等人，自然 2015）。 Teixobactin目前正在为重要革兰氏阳性AMR感染提供辅助发展例如MRSA细菌血症。我们最近发现了另一种天然产品抗生素Darobactin，带有反对革兰氏阴性AMR病原体的异常低抗性发展。尽管这些令人鼓舞，但考虑了同一发现的重新发现花费产生物种和化合物。我们认为，通过我们的方法将为应对AMR危机提供新型抗生素的访问。巴西雨林有动植物的多样性最高，我们希望微生物相同。的确，微生物直接或松散地与真核生物结合，并降解其产品。这个项目的目标是为了评估巴西的微生物多样性的土壤，以筛选革兰氏阴性化合物的分离株活性，并分离和验证新型抗菌剂。如果我们能够从土壤中找到新颖的抗菌剂新英格兰，可以合理的期望，一旦我们访问环境，发现的步伐将会有所提高地球上最富有的多样性。该项目汇集了东北大学Kim Lewis博士，耐药性专家 Drug Discovery和天然产品化学专家Sao Paulo大学Monica Pupo博士。这些科学家合作编写了该提案，并将与其执行紧密合作。