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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.

抽象的我们目前正经历抗菌素耐药性危机，世界卫生组织确定了需要将对抗耐药革兰氏阴性病原体视为“关键”。最后一类化合物作用于革兰氏阴性细菌于 50 多年前被引入。预防抗菌素耐药性的最有效策略是引入新化合物，对抗 AMR 病原体，产生耐药性的可能性很低。我们最近发现了一本小说抗菌剂 teixobactin，对革兰氏阳性菌没有可检测到的耐药性（Ling 等人，Nature 2015）。 Teixobactin 目前正处于针对重要革兰氏阳性 AMR 感染的 IND 开发阶段例如MRSA菌血症。我们最近发现了另一种天然产物抗生素，darobactin，针对革兰氏阴性 AMR 病原体的异常低耐药性发展。虽然这些都是令人鼓舞的进步，但仍需付出相当大的努力来重新发现同样的东西。产生物种和化合物。我们认为，用我们的技术来挖掘巴西土壤的丰富多样性方法将提供新型抗生素来应对抗菌素耐药性危机。巴西雨林有植物和动物具有最高的多样性，我们预计微生物也是如此。的确，微生物直接或松散地与真核生物结合，并降解其产物。该项目的目标是评估巴西土壤的微生物多样性，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药物。如果我们能够从土壤中找到新型抗菌剂新英格兰，一旦我们进入某个环境，我们可以合理地预期发现的速度将会加快拥有地球上最丰富的多样性。该项目汇集了东北大学 Kim Lewis 博士，他是耐药性和耐药性方面的专家。药物发现，以及圣保罗大学天然产物化学专家 Monica Pupo 博士。这些科学家们合作撰写了该提案，并将在执行过程中密切合作。