Evidence map›Paper›PMID 30954530›Full record

ArticleiScience2019

Two New Plasmid Post-segregational Killing Mechanisms for the Implementation of Synthetic Gene Networks in Escherichia coli.

Alex J H Fedorec, Tanel Ozdemir, Anjali Doshi, Yan-Kay Ho, Luca Rosa, Jack Rutter, Oscar Velazquez, Vitor B Pinheiro, Tal Danino, Chris P Barnes

Abstract read
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
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

35 citing papers in PubMed.

  1. Article
  2. Systems metabolic engineering for hydroxytyrosol production inApplied and environmental microbiology · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Construction of antibiotic-free riboflavin producer inSynthetic and systems biotechnology · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Chromosomal engineering of inducible isopropanol- butanol-ethanol production inFrontiers in bioengineering and biotechnology · 2023
    Article
  20. Article
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

10 authors.

Alex J H FedorecDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK; Centre for Mathematics, Physics and Engineering in the Life Sciences and Experimental Biology, University College London, London WC1E 6BT, UK. Electronic address: alexander.fedorec.13@ucl.ac.uk.
Tanel OzdemirDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Anjali DoshiDepartment of Biomedical Engineering, Columbia University, New York City, NY 10027, USA.
Yan-Kay HoInstitute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK.
Luca RosaDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Jack RutterDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Oscar VelazquezDepartment of Biomedical Engineering, Columbia University, New York City, NY 10027, USA.
Vitor B PinheiroInstitute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK; KU Leuven Rega Institute for Medical Research, Herestraat, 49 Box 1030, 3000 Leuven, Belgium.
Tal DaninoDepartment of Biomedical Engineering, Columbia University, New York City, NY 10027, USA; Data Science Institute, Columbia University, New York, NY 10027, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Chris P BarnesDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK; Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK. Electronic address: christopher.barnes@ucl.ac.uk.

Funding

Programmable Probiotics for CancerR00CA197649 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DANINO, TAL · 2016 to 2018
$651k
Programmable Probiotics for CancerK99CA197649 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DANINO, TAL · 2015 to 2015
$85k
NCI NIH HHS K99 CA197649NCI NIH HHS R00 CA197649Wellcome Trust 209409/Z/17/Z
6 · The paper itself

Abstract

Plasmids are the workhorse of both industrial biotechnology and synthetic biology, but ensuring they remain in bacterial cells is a challenge. Antibiotic selection cannot be used to stabilize plasmids in most real-world applications, and inserting dynamical gene networks into the genome remains challenging. Plasmids have evolved several mechanisms for stability, one of which, post-segregational killing (PSK), ensures that plasmid-free cells do not survive. Here we demonstrate the plasmid-stabilizing capabilities of the axe/txe toxin-antitoxin system and the microcin-V bacteriocin system in the probiotic bacteria Escherichia coli Nissle 1917 and show that they can outperform the commonly used hok/sok. Using plasmid stability assays, automated flow cytometry analysis, mathematical models, and Bayesian statistics we quantified plasmid stability in vitro. Furthermore, we used an in vivo mouse cancer model to demonstrate plasmid stability in a real-world therapeutic setting. These new PSK systems, plus the developed Bayesian methodology, will have wide applicability in clinical and industrial biotechnology.

Indexed as

BioengineeringBiological SciencesGene Network

Identifiers

PMID30954530
PMCPMC6489366

What OpenQuestion holds

Textmetadata
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.