Evidence map›Paper›PMID 23372704›Full record

ArticlePloS one2013

Cysteine depletion causes oxidative stress and triggers outer membrane vesicle release by Neisseria meningitidis; implications for vaccine development.

Bas van de Waterbeemd, Gijsbert Zomer, Jan van den Ijssel, Lonneke van Keulen, Michel H Eppink, Peter van der Ley, Leo A van der Pol

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

42 citing papers in PubMed, 89 citations in OpenAlex.

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  13. Pathogens and global health · 2023
    Review
  14. Article
  15. Review
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  17. Toxins · 2021
    Article
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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

7 authors at 2 institutions in 1 country.

Bas van de WaterbeemdVaccinology, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. bas.van.de.waterbeemd@rivm.nl
Gijsbert Zomer
Jan van den Ijssel
Lonneke van Keulen
Michel H Eppink
Peter van der Ley
Leo A van der Pol
National Institute for Public Health and the Environment · NLWageningen University & Research · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Outer membrane vesicles (OMV) contain immunogenic proteins and contribute to in vivo survival and virulence of bacterial pathogens. The first OMV vaccines successfully stopped Neisseria meningitidis serogroup B outbreaks but required detergent-extraction for endotoxin removal. Current vaccines use attenuated endotoxin, to preserve immunological properties and allow a detergent-free process. The preferred process is based on spontaneously released OMV (sOMV), which are most similar to in vivo vesicles and easier to purify. The release mechanism however is poorly understood resulting in low yield. This study with N. meningitidis demonstrates that an external stimulus, cysteine depletion, can trigger growth arrest and sOMV release in sufficient quantities for vaccine production (±1500 human doses per liter cultivation). Transcriptome analysis suggests that cysteine depletion impairs iron-sulfur protein assembly and causes oxidative stress. Involvement of oxidative stress is confirmed by showing that addition of reactive oxygen species during cysteine-rich growth also triggers vesiculation. The sOMV in this study are similar to vesicles from natural infection, therefore cysteine-dependent vesiculation is likely to be relevant for the in vivo pathogenesis of N. meningitidis.

Indexed as

Bacterial Outer Membrane ProteinsBioreactorsCell MembraneCulture MediaCysteineHumansIron-Sulfur ProteinsMeningococcal InfectionsMeningococcal VaccinesNeisseria meningitidis, Serogroup BOxidative StressProteomeBacterial Outer Membrane ProteinsCulture MediaCysteineIron-Sulfur ProteinsMeningococcal VaccinesProteome

Identifiers

PMID23372704
PMCPMC3553081
OpenAlexW1974844310

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.