Evidence map›Paper›PMID 35449016›Full record

ArticleMicrobial cell factories2022

Engineering a suite of E. coli strains for enhanced expression of bacterial polysaccharides and glycoconjugate vaccines.

Emily J Kay, Marta Mauri, Sam J Willcocks, Timothy A Scott, Jon Cuccui, Brendan W Wren

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Stepwise Assembly of theBiochemistry · 2026
    Article
  2. Review
  3. Investigation of the essential role of capsular polysaccharide in serotype 1Frontiers in cellular and infection microbiology · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Escherichia coli in the production of biopharmaceuticals.Biotechnology and applied biochemistry · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Construction of anFrontiers in bioengineering and biotechnology · 2024
    Article
  12. Article
  13. A bioconjugate vaccine againstFrontiers in bioengineering and biotechnology · 2023
    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

6 authors at 1 institution in 1 country.

Emily J KayDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Marta MauriDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Sam J WillcocksDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Timothy A ScottDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Jon CuccuiDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Brendan W WrenDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK. brendan.wren@lshtm.ac.uk.ORCID http://orcid.org/0000-0002-6140-9489
London School of Hygiene & Tropical Medicine · GB

Funding

Biotechnology and Biological Sciences Research Council BB/N001591/1Biotechnology and Biological Sciences Research Council BB/R008124/1Biotechnology and Biological Sciences Research Council BB/S004963/1
6 · The paper itself

Abstract

backgroundGlycoengineering, in the biotechnology workhorse bacterium, Escherichia coli, is a rapidly evolving field, particularly for the production of glycoconjugate vaccine candidates (bioconjugation). Efficient production of glycoconjugates requires the coordinated expression within the bacterial cell of three components: a carrier protein, a glycan antigen and a coupling enzyme, in a timely fashion. Thus, the choice of a suitable E. coli host cell is of paramount importance. Microbial chassis engineering has long been used to improve yields of chemicals and biopolymers, but its application to vaccine production is sparse.

resultsIn this study we have engineered a family of 11 E. coli strains by the removal and/or addition of components rationally selected for enhanced expression of Streptococcus pneumoniae capsular polysaccharides with the scope of increasing yield of pneumococcal conjugate vaccines. Importantly, all strains express a detoxified version of endotoxin, a concerning contaminant of therapeutics produced in bacterial cells. The genomic background of each strain was altered using CRISPR in an iterative fashion to generate strains without antibiotic markers or scar sequences.

conclusionsAmongst the 11 modified strains generated in this study, E. coli Falcon, Peregrine and Sparrowhawk all showed increased production of S. pneumoniae serotype 4 capsule. Eagle (a strain without enterobacterial common antigen, containing a GalNAc epimerase and PglB expressed from the chromosome) and Sparrowhawk (a strain without enterobacterial common antigen, O-antigen ligase and chain length determinant, containing a GalNAc epimerase and chain length regulators from Streptococcus pneumoniae) respectively produced an AcrA-SP4 conjugate with 4 × and 14 × more glycan than that produced in the base strain, W3110. Beyond their application to the production of pneumococcal vaccine candidates, the bank of 11 new strains will be an invaluable resource for the glycoengineering community.

Indexed as

Escherichia coliGlycoconjugatesBacterial VaccinesPolysaccharidesPolysaccharides, BacterialRacemases and EpimerasesStreptococcus pneumoniaeVaccines, ConjugateBacterial VaccinesGlycoconjugatesPolysaccharidesPolysaccharides, BacterialRacemases and EpimerasesVaccines, ConjugateBiological conjugationGlycoconjugatesGlycoengineeringPglBStreptococcus pneumoniaeVaccine

Identifiers

PMID35449016
PMCPMC9026721
OpenAlexW4224218935

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.