» Articles » PMID: 26641934

'Deadman' and 'Passcode' Microbial Kill Switches for Bacterial Containment

Overview
Journal Nat Chem Biol
Date 2015 Dec 8
PMID 26641934
Citations 127
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Design and regulation of engineered bacteria for environmental release.

Chemla Y, Sweeney C, Wozniak C, Voigt C Nat Microbiol. 2025; 10(2):281-300.

PMID: 39905169 DOI: 10.1038/s41564-024-01918-0.


Environment signal dependent biocontainment systems for engineered organisms: Leveraging triggered responses and combinatorial systems.

Varma S, Gulati K, Sriramakrishnan J, Ganla R, Raval R Synth Syst Biotechnol. 2025; 10(2):356-364.

PMID: 39830078 PMC: 11741035. DOI: 10.1016/j.synbio.2024.12.005.


Quadruplet codon decoding-based versatile genetic biocontainment system.

Choi Y, Kim D, Lee S, Shin Y, Lee J Nucleic Acids Res. 2025; 53(1.

PMID: 39777466 PMC: 11705086. DOI: 10.1093/nar/gkae1292.


Biological Switches: Past and Future Milestones of Transcription Factor-Based Biosensors.

De Paepe B, De Mey M ACS Synth Biol. 2024; 14(1):72-86.

PMID: 39709556 PMC: 11745168. DOI: 10.1021/acssynbio.4c00689.


Influence of Environmental Conditions on the Escape Rates of Biocontained Genetically Engineered Microbes.

Hartig A, Dai W, Zhang K, Kapoor K, Rottinghaus A, Moon T Environ Sci Technol. 2024; 58(51):22657-22667.

PMID: 39668804 PMC: 11750180. DOI: 10.1021/acs.est.4c10893.


References
1.
Csorgo B, Feher T, Timar E, Blattner F, Posfai G . Low-mutation-rate, reduced-genome Escherichia coli: an improved host for faithful maintenance of engineered genetic constructs. Microb Cell Fact. 2012; 11:11. PMC: 3280934. DOI: 10.1186/1475-2859-11-11. View

2.
Wright O, Stan G, Ellis T . Building-in biosafety for synthetic biology. Microbiology (Reading). 2013; 159(Pt 7):1221-1235. DOI: 10.1099/mic.0.066308-0. View

3.
Cameron D, Collins J . Tunable protein degradation in bacteria. Nat Biotechnol. 2014; 32(12):1276-81. PMC: 4262603. DOI: 10.1038/nbt.3053. View

4.
Bell C, Lewis M . A closer view of the conformation of the Lac repressor bound to operator. Nat Struct Biol. 2000; 7(3):209-14. DOI: 10.1038/73317. View

5.
Rovner A, Haimovich A, Katz S, Li Z, Grome M, Gassaway B . Recoded organisms engineered to depend on synthetic amino acids. Nature. 2015; 518(7537):89-93. PMC: 4590768. DOI: 10.1038/nature14095. View