S144: Rewiring Quorum Sensing Signaling Yields Autonomous Localization and Actuation of Engineered Cells

Synthetic biology is often attributed to the rewiring of a cell’s genetic circuitry for the synthesis of novel products using heterologous processes. A less common but equally innovative view makes use of the reprogrammed cell as the product. We have interrogated the native autoinducer-2 signal transduction process of created a series of genetic circuits that when appropriately assembled in vivo endows E. coli with targeting, sensing & switching capabilities. The resultant cell autonomously navigates and carries or deploys important “cargo”. The bacteria target desired locales on mammalian cell surfaces by “homing” functions which bind cell surface biomarkers, receptors or other ligands. Specifically, a IgG Fc region binding domain, protein G, is displayed on the outer membrane of bacteria which allows targeting. Upon accumulation at the targeted surface they trigger a “switch” in response to the biomarker density. This serves as a phenotype focusing system and maintains the switch in an “off” state until the desired threshold is reached. Importantly, by genetically altering effectors of the luxS regulon (e.g., repressor, LsrR; kinase, LsrK; transporter, LsrACDB; and AI-2 effectors, LsrFG), this threshold are be “tuned” for desired applications; several potential applications are discussed.