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

Molecular Systems Biology

Hsuan-Chen Wu¹  Chen-Yu Tsao¹  David N Quan¹  Yi Cheng⁵  Matthew D Servinsky²  Karen K Carter⁴  Kathleen J Jee¹  Jessica L Terrell¹  Amin Zargar⁴  Gary W Rubloff⁵  Gregory F Payne¹  James J Valdes³ 

[1] Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA;Sensors and Electron Devices Directorate, US Army Research Laboratory, Adelphi, MD, USA;US Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, MD, USA;Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD, USA;Department of Material Science and Engineering, University of Maryland, College Park, MD, USA

关键词: cancer;    EGFR;    Escherichia coli;    quorum sensing;    synthetic biology;   

DOI  :  10.1038/msb.2012.71

来源: Wiley

【 摘 要 】

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.

Synopsis

Escherichia coli were engineered to enable programmed motility, sensing and phenotypic response to the density of epidermal growth factor receptor expressed on the surface of cancer cells.

• Bacteria were engineered to display targeted motility through AI-2-mediated chemotaxis.
• Recruitment of motile bacteria was achieved by site-specific synthesis of quorum sensing autoinducers using anti-EGFR nanofactories.
• Threshold-based switching of bacterial gene expression was controlled by AI-2 quorum sensing.
• The engineered ‘bacterial dirigible’ represents a new means for targeted drug delivery and may have multiple applications wherein bacterial cells are designed to carry out specified tasks.

【 授权许可】

CC BY-NC-SA   
Copyright © 2013 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.