Autonomous bacterial localization and gene expression based on nearby cell receptor density.

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TitleAutonomous bacterial localization and gene expression based on nearby cell receptor density.
Publication TypeJournal Article
Year of Publication2013
AuthorsWu, H-C, Tsao, C-Y, Quan, DN, Cheng, Y, Servinsky, MD, Carter, KK, Jee, KJ, Terrell, JL, Zargar, A, Rubloff, GW, Payne, GF, Valdes, JJ, Bentley, WE
JournalMol Syst Biol
Volume9
Pagination636
Date Published01/22/2013
ISSN1744-4292
KeywordsCell Line, Tumor, Drug Delivery Systems, Escherichia coli, Gene Expression Regulation, Genetic Engineering, Head and Neck Neoplasms, Homoserine, Humans, Lactones, Nanotechnology, Quorum Sensing, Receptor, Epidermal Growth Factor
Abstract

Escherichia coli were genetically modified to enable programmed motility, sensing, and actuation based on the density of features on nearby surfaces. Then, based on calculated feature density, these cells expressed marker proteins to indicate phenotypic response. Specifically, site-specific synthesis of bacterial quorum sensing autoinducer-2 (AI-2) is used to initiate and recruit motile cells. In our model system, we rewired E. coli's AI-2 signaling pathway to direct bacteria to a squamous cancer cell line of head and neck (SCCHN), where they initiate synthesis of a reporter (drug surrogate) based on a threshold density of epidermal growth factor receptor (EGFR). This represents a new type of controller for targeted drug delivery as actuation (synthesis and delivery) depends on a receptor density marking the diseased cell. The ability to survey local surfaces and initiate gene expression based on feature density represents a new area-based switch in synthetic biology that will find use beyond the proposed cancer model here.

DOI10.1038/msb.2012.71
Alternate JournalMol. Syst. Biol.
PubMed ID23340842
PubMed Central IDPMC3564257