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Discovery of antibiotics active against multidrug resistant bacteria

发现对多重耐药细菌具有活性的抗生素

基本信息

批准号：
8866795
负责人：
Roberto G. Kolter
金额：
$ 25.43万
依托单位：
HARVARD MEDICAL SCHOOL
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：
2015-04-10 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8866795
关键词：
Actinobacteria class Actinomycetales Agar Anti-Bacterial Agents Antibiotic Resistance Antibiotics Bacteria Bacterial Antibiotic Resistance Biological Biological Assay Coculture Techniques Color Communicable Diseases Communities Complex Conditioned Culture Media Culture Media Culture Techniques Development Diffuse Environment Evolution Exhibits Glean Goals Growth History of Medicine Human Individual Infection Klebsiella pneumonia bacterium Life Liquid substance Methods Mind Minor Multi-Drug Resistance Nature Nuclear Magnetic Resonance Nutrient Production Resistance Ribosomal RNA Sampling Sepharose Source Staphylococcus aureus Techniques Testing Therapeutic Agents Time antimicrobial base carbapenem resistance clinically relevant genome sequencing high throughput screening insight interest killings liquid chromatography mass spectrometry methicillin resistant Staphylococcus aureus method development multi-drug resistant pathogen novel novel strategies pathogen pathogenic bacteria public health relevance research study resistant strain small molecule

项目摘要

DESCRIPTION (provided by applicant): The discovery of antibiotics and their development into therapeutic agents represents one of the most important advances in the history of medicine. However, the evolution of antibiotic resistance is greatly limiting antibiotic usefulness The specter of a post-antibiotic era looms heavy in the field of infectious diseases. Thus, there is an urgent need new antibiotics that are effective against important human pathogens that are now resistant to most, if not all, commonly used antibiotics. Bacteria from the order Actinomycetales have been the most important source of antibiotics. Yet, while the sequenced genomes of these bacteria suggest that there they have the potential to produce many more antibiotic molecules, only a fraction of the predicted molecules have been detected in the lab. In contrast to most culturing techniques that involve only one species, we have discovered that culturing bacteria in multi-species communities stimulates the production of diverse and unique small molecules. With this in mind, in order to stimulate the production of novel antimicrobial compounds, we have developed a method for growing complex multi-species communities over extended periods of time. These communities are grown in an environment that allows them to secrete molecules into a liquid medium that can easily be sampled and assayed for the production of antibiotics that are effective against pathogens such as methicillin resistant Staphylococcus aureus (MRSA) and carbapenem resistant Klebsiella pneumoniae. We specifically propose to develop a large-scale screen for the discovery of novel antibiotic activities produced by Actinomycetes grown as multi-species communities. We also propose to identify and optimize the production of the molecules that display antibiotic activity. These aims will hopefully result in the identification of new antibiotics that are effective against currently problematic multi-drug resistant pathogens.