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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：
9890152
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/9890152
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 Recombinant DNA Recovery Resistance Resistance development Resources 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 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.

摘要我们目前正在经历一场抗菌素耐药性危机，世界卫生组织确定了需要将对抗耐药性革兰氏阴性病原体作为“关键”。最后一类化合物作用于革兰氏阴性菌是50多年前引入的。预防抗菌素耐药性的最有效策略是引入新的化合物，对AMR病原体起作用，并且产生耐药性的可能性低。我们最近发现了一本小说抗微生物剂，teixobactin，其对革兰氏阳性细菌没有可检测的抗性（Ling等人，性质 2015年）。Teixobactin目前正处于IND开发阶段，可针对重要的革兰氏阳性AMR感染例如MRSA菌血症。我们最近发现了另一种天然产物抗生素darobactin，对革兰氏阴性AMR病原体产生异常低的耐药性。虽然这些都是令人鼓舞的进步，但在重新发现相同的方面花费了相当大的努力。产生物种和化合物。我们的理由是，利用我们丰富多样的巴西土壤，这些方法将提供获得新型抗生素的途径，以应对AMR危机。巴西的热带雨林最高的植物和动物的多样性，我们希望微生物也是如此。的确，微生物直接或松散地与真核生物结合，并降解它们的产物。这个项目的目标评估巴西土壤的微生物多样性，筛选革兰氏阴性菌的化合物，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的抗菌剂，在新英格兰，我们有理由期待，一旦我们进入一个环境，拥有地球上最丰富的物种多样性。该项目汇集了东北大学的耐药性专家金刘易斯博士和药物发现，以及圣保罗大学的Monica Pupo博士，天然产物化学专家。这些科学家们合作编写了该提案，并将密切合作执行该提案。