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Synthetic biology

Genetic kill switches — a matter of life or death

Nature Reviews Genetics volume 17, page 67 (2016)Cite this article

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The applications of genetically engineered bacteria are diverse and ever-expanding, but the possibility that these organisms escape confinement poses an environmental threat. Therefore, several approaches have been developed to make bacterial survival dependent on the presence of non-native or non-natural components in the culture medium. However, some of these approaches could fail if the metabolites required for growth are unexpectedly present in uncontrolled environments, and those in which the bacterial genome needs to be modified on a large scale might be impractical and cumbersome.

The first strategy, dubbed 'Deadman', relies on a circuit in which the LacI and TetR transcription factors are reciprocally repressive, but in which the expression of TetR is favoured owing to modifications in the strength of the ribosomal binding sites of the two transcription factors. Inhibition of TetR expression by anhydrotetracycline (ATc), a compound that is not normally found in nature, is necessary for expression of LacI. LacI directly inhibits expression of a lethal toxin and/or indirectly prevents inhibition of the expression of an essential gene; these effects, either alone or combined in a single circuit, keep the cells alive. Removal of ATc from the environment activates the expression of TetR, which leads to cell death. A 'fail-safe' mechanism was also added to the system, whereby production of the toxin and cell death are independently activated by isopropyl β-D-1-thiogalactopyranoside (IPTG).

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References

  1. Chan, C. T. et al. 'Deadman' and 'Passcode' microbial kill switches for bacterial containment. Nat. Chem. Biol. http://dx.doi.org/10.1038/nchembio.1979 (2015

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Authors
  1. Joana Osório
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Osório, J. Genetic kill switches — a matter of life or death. Nat Rev Genet 17, 67 (2016). https://doi.org/10.1038/nrg.2015.29

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