STTR Phase II: An Advanced Antibiotic Screen of Marine Environmental DNA through a Metabolically Engineered E. coli Strain

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). This Small Business Technology Transfer (STTR) Phase II project offers a novel route to finding critically needed new antibiotics. The emergence of antibiotic-resistant bacterial pathogens is a growing medical challenge, urgently requiring new drugs. Natural products, synthesized primarily by environmental microorganisms, have supplied most of the current arsenal of effective antibiotics. However, the discovery rate of new antibiotics has greatly diminished. With the recent understanding that the vast majority of environmental microorganisms have never been screened for the production of antibiotics because they cannot be easily cultured in the laboratory, EarthGenes has developed a technology to access these organisms, involving extracting environmental DNA, cloning large fragments into specialized vectors to create DNA libraries, expressing these libraries in suitable easily-grown surrogate hosts, and screening the libraries for antibiotics encoded by the environmental DNA. Professor Blaine Pfeifer at Tufts University has developed the most advanced bacterial host for expressing environmental DNA, potentially improving the efficiency of this technology. Thus, the EarthGenes-Tufts collaboration is designed to lead to the discovery of new, more potent antibiotic drugs. The broader impacts of this research include a technology to provide a new, continuous supply of potent antibiotics to treat infectious diseases, thus addressing a critical health-related goal with technical innovation. The technology can also be extended to other disease areas. The impact is augmented by education and outreach, including the education of undergraduates, graduate students, and postdoctoral associates, with mechanisms in place to attract underrepresented students from diverse backgrounds.