SBIR-STTR Award

The prevalence of antibiotic resistant bacteria has risen dramatically over the past decades with over 70% of hospital bacterial infections harboring resistance to one or more classes of antibiotics. To date, the rise of drug resistant pathogens has been addressed by improved containment practices, judicious use of antibiotic treatments, and government-sponsored antibiotic research and development programs. Despite these measures, we are still facing a losing battle against the spread of antibiotic resistance. Given these significant challenges, both technical and economic, new strategies for combating antibiotic resistance are desperately needed. We propose a novel strategy that will limit the occurrence and spread of antibiotic resistance by targeting the genetic elements that encode antibiotic resistance, rather than any particular microbial species or strain. The approach is therefore broadly applicable to both Gram-positive and negative bacteria. To achieve this goal, we propose to use engineered mobile genetic elements to"vaccinate"microbial communities against uptake and dissemination of genetically-encoded antibiotic resistance elements. This approach is now made possible by technology advances in synthetic biology centered around gene and genome design and construction.

Keywords:
Synthetic Biology, Mobile Genetic Elements, Antibiotic Resistance, Antibiotic Control

Next generation sequencing technologies are allowing researchers to rapidly and accurately interrogate the genomic content of microbiomes. Advances in our understanding of the human microbiome are likely to lead to the use of next generation sequencing as a diagnostic tool to identify the existence and precise genotype of pathogens and virulence genes. Likewise, our ability to engineer microbes using synthetic biology tools and technologies has advanced to the point where we can begin to consider applying engineered microbes to restore healthy microbiome states. Engineered organisms are already used widely in human health for therapeutic production, biomedical research, and more recently as products themselves. This SBIR Phase II proposal outlines the opportunity to merge the fields of microbiome discovery and organism engineering to create new strategies for modulating human health and disease: via engineered probiotics. We describe engineered microbes with the potential to 1) target specific pathogens based on sequence data, 2) destroy targeted gene sequences, 3) and avoid the use of traditional antibiotics. The performance of this system will be demonstrated in an in vivo mouse model.

Keywords:
Synthetic Biology, Mobile Genetic Elements, Crisprs,