'Deadman' and 'Passcode' microbial kill switches for bacterial containment

Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill...

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Bibliographic Details
Main Authors: Bashor, Caleb, Collins, James J., Chan, Clement T. Y., Lee, Jeongwook, Cameron, Douglas
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Language:en_US
Published: Nature Publishing Group 2017
Online Access:http://hdl.handle.net/1721.1/108106
https://orcid.org/0000-0002-5560-8246
https://orcid.org/0000-0003-0705-0177
Description
Summary:Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival. The Passcode kill switch uses a similar two-layered transcription design and incorporates hybrid LacI-GalR family transcription factors to provide diverse and complex environmental inputs to control circuit function. These synthetic gene circuits efficiently kill Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism.