Evidence map›Paper›PMID 28742139›Full record

ArticlePLoS pathogens2017

Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.

Elise S Hovingh, Bryan van den Broek, Betsy Kuipers, Elena Pinelli, Suzan H M Rooijakkers, Ilse Jongerius

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

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  16. Frontiers in cellular and infection microbiology · 2020
    Review
  17. Comparative Integrated Omics Analysis of the Hfq Regulon inInternational journal of molecular sciences · 2019
    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

6 authors at 2 institutions in 1 country.

Elise S HovinghDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Bryan van den BroekDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-0192-4788
Betsy KuipersCentre for Infectious Disease Control, National institute for Public Health and the Environment, Bilthoven, The Netherlands.
Elena PinelliCentre for Infectious Disease Control, National institute for Public Health and the Environment, Bilthoven, The Netherlands.
Suzan H M RooijakkersDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Ilse JongeriusDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-7759-9897
University Medical Center Utrecht · NLNational Institute for Public Health and the Environment · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.

Indexed as

Bacterial ProteinsBordetella pertussisComplement C1Complement C2Complement C4HumansVirulenceVirulence Factors, BordetellaWhooping CoughBacterial ProteinsComplement C1Complement C2Complement C4Virulence Factors, Bordetella

Identifiers

PMID28742139
PMCPMC5542704
OpenAlexW2738485176

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.