Microbial symbionts of marine invertebrates for antibiotic discovery

用于抗生素发现的海洋无脊椎动物的微生物共生体

基本信息

批准号：
8978558
负责人：
Amy Lynn Spoering
金额：
$ 22.44万
依托单位：
NOVOBIOTIC PHARMACEUTICALS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8978558
关键词：
Address Agar Anabolism Animal Sources Antibiotics Antineoplastic Agents Back Bacteria Bacterial Infections Cell Wall Cells Chemicals Collaborations Communities Daptomycin Development Devices Diffuse Diffusion Drug resistance Environment Escherichia coli Floor G-Quartets Goals Growth Growth Factor In Situ Incubated Industry Invertebrates Life Linezolid Marine Invertebrates Marines Massachusetts Membrane Methodology Methods Microbe Mycobacterium tuberculosis National Cancer Institute Nature Organism Peptide Hydrolases Phase Phylogenetic Analysis Property Resources Sea Series Source Staphylococcus aureus Sterility Symbiosis Techniques Technology Testing Therapeutic Urochordata Vancomycin resistant enterococcus Variant Water antimicrobial base combat coral design feeding inhibitor/antagonist invertebrate host methicillin resistant Staphylococcus aureus microbial microorganism new technology novel pathogen public health relevance rRNA Genes screening seal success tumor

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to discover novel antibiotics to combat important drug-resistant pathogens. One effective countermeasure against such pathogens is novel antibiotics, but the rate of antibiotic discovery has been in steady decline. All the more recently introduced antibiotics are derivatives of older antibiotics or resulted from revival of initially discarded compounds which were discovered decades ago such as daptomycin, linezolid, synercid and fidaxomycin. Clinically used antibiotics have traditionally been discovered by screening for active secondary metabolites of readily culturable microorganisms. This resource represents <1% of all microbial diversity in nature. The other >99% unexplored, and previously unavailable, microorganisms are arguably the single most promising resource for novel antibiotics. NovoBiotic directly addresses the bottleneck of antibiotic discovery by using unique cultivation approaches: the diffusion chamber and trap methodologies to isolate previously "uncultivable" microorganisms. This approach has resulted in 25 new compounds so far, at a rate far higher than the predicted industry standard. Several of these compounds are of principal novelty and are in development including Novo10, a DNA G-quadruplex binder, currently in development as an anti-cancer agent in collaboration with the National Cancer Institute; Novo22, a macrolactam inhibitor of cell wall biosynthesis; lassomycin, an inhibitor of the essential ClpP1P2C1 protease of M. tuberculosis; and teixobactin, a novel cell wall synthesis inhibitor. This project takes the next step and extends the technology to shallow water marine invertebrate- microbe symbioses, ubiquitously present and easily accessible in local communities. From the limited exploration conducted to date, a number of bioactive compounds with unique properties have been discovered from marine symbioses, including anti-tumor and anti-microbial compounds. There is strong evidence that it is the associated microorganisms living in association with the host invertebrates that produce the bioactive compounds. We will develop our methods to isolate novel microbial species living in association with marine invertebrates and screen these strains for antimicrobial activity. We will compare the diversity and novelty of active compounds from strains isolated from the diffusion chamber, trap and conventional plating. The end result of this Phase I project will be proof of concept of new technologies to discover antibiotics from a poorly explored source of microbial diversity: formerly "uncultivable" microbial species from marine invertebrate-microbe symbioses.

描述（由申请人证明）：该项目的总体目标是发现新颖的诺比特IMBAT重要的耐药病原体。最近，由于几十年前，涵盖了临床使用的抗生素，因此引入了较旧的抗生素，或者是由于临床上使用的抗生素而复兴的。在自然界中的所有微生物多样性中，毫无疑问地> 99％，微生物是可用于新型抗生素的单一鉴定性。，几个原理是主要的新颖性，包括DNA G Quadlexebind。 clpp1p2c1结核分枝杆菌的蛋白酶，一种新型的细胞壁合成抑制剂。，抗微生物化合物是与生物活性化合物相关的相关微生物。传统的镀层。