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Autonomous bacterial localization and gene expression based on nearby cell receptor density.
Wu, Hsuan-Chen; Tsao, Chen-Yu; Quan, David N; Cheng, Yi; Servinsky, Matthew D; Carter, Karen K; Jee, Kathleen J; Terrell, Jessica L; Zargar, Amin; Rubloff, Gary W; Payne, Gregory F; Valdes, James J; Bentley, William E.
Afiliação
  • Wu HC; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
Mol Syst Biol ; 9: 636, 2013.
Article em En | MEDLINE | ID: mdl-23340842
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Sistemas de Liberação de Medicamentos / Escherichia coli / Receptores ErbB / Neoplasias de Cabeça e Pescoço / Homosserina / Lactonas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Syst Biol Assunto da revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Sistemas de Liberação de Medicamentos / Escherichia coli / Receptores ErbB / Neoplasias de Cabeça e Pescoço / Homosserina / Lactonas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Syst Biol Assunto da revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos