Evidence map›Paper›PMID 33430875›Full record

ArticleMicrobial cell factories2021

Protein over-expression in Escherichia coli triggers adaptation analogous to antimicrobial resistance.

Jack James, Benjamin Yarnall, Andy Koranteng, Jane Gibson, Tahmina Rahman, Declan A Doyle

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

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  11. Antibiotic-ResistantVeterinary sciences · 2022
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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

6 authors at 2 institutions in 1 country.

Jack JamesSchool of Biological Sciences, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK.
Benjamin YarnallSchool of Biological Sciences, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK.
Andy KorantengSchool of Biological Sciences, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK.
Jane GibsonCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK.
Tahmina RahmanQueen Alexandra Hospital, Portsmouth Hospital University NHS Trust, Cosham, Portsmouth, PO6 3LY, UK.
Declan A DoyleSchool of Biological Sciences, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK. D.A.Doyle@soton.ac.uk.ORCID http://orcid.org/0000-0003-4596-3292
University of Southampton · GBQueen Alexandra Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe E. coli pET system is the most widely used protein over-expression system worldwide. It relies on the assumption that all cells produce target protein and it is generally believed that integral membrane protein (IMP) over-expression is more toxic than their soluble counterparts.

resultsUsing GFP-tagged proteins, high level over-expression of either soluble or IMP targets results in > 99.9% cell loss with survival rate of only < 0.03%. Selective pressure generates three phenotypes: large green, large white and small colony variants. As a result, in overnight cultures, ~ 50% of the overall cell mass produces no protein. Genome sequencing of the phenotypes revealed genomic mutations that causes either the loss of T7 RNAP activity or its transcriptional downregulation. The over-expression process is bactericidal and is observed for both soluble and membrane proteins.

conclusionsWe demonstrate that it is the act of high-level over-expression of exogenous proteins in E. coli that sets in motion a chain of events leading to > 99.9% cell death. These results redefine our understanding of protein over-production and link it to the adaptive survival response seen in the development of antimicrobial resistance.

Indexed as

Adaptation, PhysiologicalAnti-Bacterial AgentsComputational BiologyDrug Resistance, BacterialEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialMembrane ProteinsMicrobial ViabilityMutationAnti-Bacterial AgentsEscherichia coli ProteinsMembrane ProteinsAntimicrobial resistanceBL21(DE3)Escherichia coliProtein over-expression

Identifiers

PMID33430875
PMCPMC7798265
OpenAlexW3045537844

What OpenQuestion holds

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LicenceCC BY
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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.