Evidence map›Paper›PMID 28335725›Full record

ArticleBMC evolutionary biology2017

Surface layer proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response.

Mark Lynch, Thomas A Walsh, Izabela Marszalowska, Andrew E Webb, Micheál Mac Aogain, Thomas R Rogers, Henry Windle, Dermot Kelleher, Mary J O'Connell, Christine E Loscher

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in BMC evolutionary biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 22% 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.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Microbiology (Reading, England) · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Host Immune Responses toFrontiers in microbiology · 2021
    Review
  12. S-layer Impacts the Virulence of Bacillus in Endophthalmitis.Investigative ophthalmology & visual science · 2019
    Article
  13. Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Mark LynchImmunomodulation Research Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Thomas A WalshBioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Izabela MarszalowskaImmunomodulation Research Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Andrew E WebbBioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Micheál Mac AogainDepartment of Clinical Microbiology, Trinity College Dublin, St James Hospital Dublin, Dublin, Ireland.
Thomas R RogersDepartment of Clinical Microbiology, Trinity College Dublin, St James Hospital Dublin, Dublin, Ireland.
Henry WindleInstitute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Dermot KelleherFaculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
Mary J O'ConnellBioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. m.oconnell@leeds.ac.uk.
Christine E LoscherImmunomodulation Research Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Dublin City University · IETrinity College Dublin · IEImperial College London · GBUniversity of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundClostridium difficile is a nosocomial pathogen prevalent in hospitals worldwide and increasingly common in the community. Sequence differences have been shown to be present in the Surface Layer Proteins (SLPs) from different C. difficile ribotypes (RT) however whether these differences influence severity of infection is still not clear.

resultsWe used a molecular evolutionary approach to analyse SLPs from twenty-six C. difficile RTs representing different slpA sequences. We demonstrate that SLPs from RT 027 and 078 exhibit evidence of positive selection (PS). We compared the effect of these SLPs to those purified from RT 001 and 014, which did not exhibit PS, and demonstrate that the presence of sites under positive selection correlates with ability to activate macrophages. SLPs from RTs 027 and 078 induced a more potent response in macrophages, with increased levels of IL-6, IL-12p40, IL-10, MIP-1α, MIP-2 production relative to RT 001 and 014. Furthermore, RTs 027 and 078 induced higher expression of CD40, CD80 and MHC II on macrophages with decreased ability to phagocytose relative to LPS.

conclusionsThese results tightly link sequence differences in C. difficile SLPs to disease susceptibility and severity, and suggest that positively selected sites in the SLPs may play a role in driving the emergence of hyper-virulent strains.

Indexed as

Bacterial ProteinsClostridioides difficileClostridium InfectionsHumansImmunity, InnateMacrophagesMembrane GlycoproteinsPhagocytosisPhylogenyRibotypingBacterial ProteinsMembrane GlycoproteinsS-layer proteinsClostridium difficilePositive selectionProtein evolutionProtein functional shiftSurface layer proteinVirulence

Identifiers

PMID28335725
PMCPMC5364705
OpenAlexW2598606371

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.