High throughput antibiotic discovery from the uncultivated microbial majority.
Small Business Information
NOVOBIOTIC PHARMACEUTICALS, LLC
NOVOBIOTIC PHARMACEUTICALS, LLC, 767C CONCORD AVE, CAMBRIDGE, MA, -
AbstractDESCRIPTION (provided by applicant): The long-term goal of this project is to develop novel, broad-spectrum antibiotics against both biowarfare agents and common drug resistant pathogens. The potential use of engineered, multi-drug-resistant strains as age nts of bioterrorism, and the current spread of conventional drug resistant pathogens necessitate the development of novel antibiotics. Most antibiotics in use today have been obtained from less than 1% of microbial species due to the inability to culture t he vast majority of species by current methods. The remaining 99% of species represent essentially an unlimited diversity of microorganisms to discover novel antibiotics. In this Phase I project we aim to develop an industrial-scale methodology to grow and screen previously uncultivated bacteria, including Actinobacteria, and obtain proof-of-principle for production of novel broad-spectrum antibiotics from this untapped source of secondary metabolites. To access the uncultivable species, we will capitaliz e on our proprietary method based on in situ cultivation of environmental microorganisms, followed by their domestication in vitro. To achieve this goal, we will develop the method into a unique high throughput technology platform for massive cultivation a nd identification of new antibiotics from uncultivable microorganisms. The specific aims of the project are: Aim 1: Develop ichip, the cultivation device combining hundreds of miniature diffusion chambers as a technology for a rapid, high throughput, in situ cultivation and domestication of uncultivable microorganisms; Aim 2: Identify species with broad spectrum antimicrobial activities using a panel of multidrug resistant pathogens and biowarfare agents; Aim 3: Investigate the chemical novelty of the d iscovered activities. The end product will be a pipeline for discovery of novel antimicrobials, which we will fully utilize in Phase II to develop novel broad spectrum compounds. The annual market for antimicrobials is 25 billion, and several broad-spectr um drugs have sales in excess of 1 billion. The large-scale screening in Phase II will produce a variety of candidate molecules, which will undergo detailed validation, ultimately resulting in new antibiotic products targeting this market. PUBLIC H EALTH RELEVANCE: The rapid acquisition of resistance of bacterial pathogens in both community and hospital based infections coupled with the decreased investment in novel antibiotic development by large pharmaceutical companies represents an impending publ ic health crisis. The purpose of this project is to develop a new technology to discover novel antibiotics. These new antibiotics will provide the public with a stronger defense whether the threat is from conventional or bioterror bacterial pathogens.
* information listed above is at the time of submission.