Development of Synthetic Probiotics to Detect and Eliminate Biothreat Agents
Abstract
The emerging disciplines of synthetic and systems biology offer great promise for the treatment of microbial pathogens. The ability to engineer and rewire microbial circuits sets the stage for a new generation of ‘smart’ bioactive systems capable of sensing and responding to biothreat agents. Realizing this potential will require advances in the specific recognition of target pathogens, the development of signal integration and communication circuits, and the ability to produce and release antimicrobial compounds in response to target pathogens. In this program, we are developing an integrated research platform to create synthetic probiotic agents that specifically detect and eliminate the intestinal pathogens Salmonella, Shigella, and Vibrio cholerae. Using a combination of systems biology and screening approaches, we have engineered receptors that recognize secreted and surface-exposed molecules produced by the target pathogens. These receptors have been incorporated into a signal integration system in the probiotic Lactoccocus lacti that couples the pathogen-recognition circuit with an inducible system to coordinate expression of pathogen-specific output modules. To eliminate pathogens, we are combining traditional antimicrobial peptides (AMPs) with specific and highly potent lantibiotic peptides to develop a novel class of antimicrobial compounds that are produced and released by the engineered probiotic cells. Together, this integrated research program is engineering synthetic probiotic agents with the capability to sense, respond to and destroy target pathogens.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 26, 2016
- Source ID
- HDTRA11510040
Entities
People
- James J. Collins
Organizations
- Defense Threat Reduction Agency
- Harvard University