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

作者：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^*

来源：Molecular Systems Biology, 2013, 9(1): 636.

DOI：10.1038/msb.2012.71

• cancer
• EGFR
• Escherichia coli
• quorum sensing
• synthetic biology

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 newtype 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. Molecular Systems Biology 9: 636; published online 22 January 2013; doi:10.1038/msb.2012.71

• 出版日期2013-1