title: Autonomous bacterial localization and gene expression based on nearby cell receptor density.
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.
authors: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
authors: Hsuan-Chen
authors: HC
authors: Wu
authors: Chen-Yu
authors: CY
authors: Tsao
authors: David N
authors: DN
authors: Quan
authors: Yi
authors: Y
authors: Cheng
authors: Matthew D
authors: MD
authors: Servinsky
authors: Karen K
authors: KK
authors: Carter
authors: Kathleen J
authors: KJ
authors: Jee
authors: Jessica L
authors: JL
authors: Terrell
authors: Amin
authors: A
authors: Zargar
authors: Gary W
authors: GW
authors: Rubloff
authors: Gregory F
authors: GF
authors: Payne
authors: James J
authors: JJ
authors: Valdes
authors: William E
authors: WE
authors: Bentley
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005818:Genetic Engineering / Q000379:methods; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006714:Homoserine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000378:metabolism*; D036103:Nanotechnology; D053038:Quorum Sensing
chemical_list: D007783:Lactones; C091088:N-octanoylhomoserine lactone; D006714:Homoserine; D066246:ErbB Receptors