Evidence map›Paper›PMID 35115506›Full record

ArticleNature communications2022

Genetically stable CRISPR-based kill switches for engineered microbes.

Austin G Rottinghaus, Aura Ferreiro, Skye R S Fishbein, Gautam Dantas, Tae Seok Moon

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
16.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 215 citations in OpenAlex.

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  11. Living Microbial Drugs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
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66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Austin G Rottinghaus *Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Aura Ferreiro *The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4022-2460
Skye R S FishbeinThe Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Gautam DantasThe Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. dantas@wustl.edu.ORCID http://orcid.org/0000-0003-0455-8370
Tae Seok MoonDepartment of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, MO, USA. tsmoon@wustl.edu.ORCID http://orcid.org/0000-0001-8373-9051
Washington University in St. Louis · US

Funding

Tunable therapeutic modulation of the gut microbiome by engineered probioticsR01AT009741 · NCCIH · WASHINGTON UNIVERSITY · PI DANTAS, GAUTAM, MOON, TAE SEOK · 2018 to 2022
$3.5M
NCCIH NIH HHS R01 AT009741
6 · The paper itself

Abstract

Microbial biocontainment is an essential goal for engineering safe, next-generation living therapeutics. However, the genetic stability of biocontainment circuits, including kill switches, is a challenge that must be addressed. Kill switches are among the most difficult circuits to maintain due to the strong selection pressure they impart, leading to high potential for evolution of escape mutant populations. Here we engineer two CRISPR-based kill switches in the probiotic Escherichia coli Nissle 1917, a single-input chemical-responsive switch and a 2-input chemical- and temperature-responsive switch. We employ parallel strategies to address kill switch stability, including functional redundancy within the circuit, modulation of the SOS response, antibiotic-independent plasmid maintenance, and provision of intra-niche competition by a closely related strain. We demonstrate that strains harboring either kill switch can be selectively and efficiently killed inside the murine gut, while strains harboring the 2-input switch are additionally killed upon excretion. Leveraging redundant strategies, we demonstrate robust biocontainment of our kill switch strains and provide a template for future kill switch development.

Indexed as

AnimalsAnti-Bacterial AgentsCRISPR-Cas SystemsEscherichia coliFemaleGene Expression RegulationGenetic EngineeringMiceMice, Inbred C57BLMicrobial ViabilityProbioticsSOS Response, GeneticsStreptomycinTemperatureTetracyclines4-epianhydrotetracyclineAnti-Bacterial AgentsStreptomycinTetracyclines

Identifiers

PMID35115506
PMCPMC8813983
OpenAlexW4210628575

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.