Evidence map›Paper›PMID 34506615›Full record

ArticlePLoS pathogens2021

A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis.

Junyan Liu, Hubertine M E Willems, Emily A Sansevere, Stefanie Allert, Katherine S Barker, David J Lowes, Andrew C Dixson, Zhenbo Xu, Jian Miao, Christian DeJarnette and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Phenotypic and genotypic analysis ofInfection and immunity · 2026
    Article
  3. Article
  4. Article
  5. Hemolytic Activity of VaginalPathogens (Basel, Switzerland) · 2026
    Article
  6. Article
  7. mBio · 2026
    Article
  8. International journal of molecular sciences · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Commensal colonization ofMicrobiology spectrum · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Microorganisms · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Review
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

17 authors at 4 institutions in 4 countries.

Junyan LiuSchool of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou, China.
Hubertine M E WillemsDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Emily A SansevereDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Stefanie AllertDepartment of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
Katherine S BarkerDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0002-3824-6829
David J LowesDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0003-0401-6790
Andrew C DixsonDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, United States of America.ORCID 0000-0003-0227-653X
Zhenbo XuSchool of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou, China.ORCID 0000-0003-2865-2441
Jian MiaoSchool of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou, China.
Christian DeJarnetteIntegrated Program in Biomedical Sciences, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0002-9733-9152
Helene TournuDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Glen E PalmerDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Jonathan P RichardsonCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom.
Francisco N BarreraDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, United States of America.
Bernhard HubeDepartment of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.ORCID 0000-0002-6028-0425
Julian R NaglikCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom.ORCID 0000-0002-8072-7917
Brian M PetersDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0002-0445-2077
University of Tennessee Health Science Center · USKing's College London · GBLeibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) · DEUniversity of Tennessee at Knoxville · US

Funding

Candidalysin: a key mediator of Candida vaginitis immunopathologyR01AI134796 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI Brian M Peters · 2018 to 2026
$2.9M
Cellular, Biochemical and Molecular Sciences Training ProgramT32GM137793 · NIGMS · VANDERBILT UNIVERSITY · PI Katherine Louise Friedman, TODD R GRAHAM · 2021 to 2026
$2.6M
IL-17 Receptor Signaling in the Oral MucosaR01DE022550 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GAFFEN, SARAH L · 2012 to 2016
$2.1M
Transmembrane Peptides for Targeting Acidosis - Equipment SupplementR01GM120642 · NIGMS · UNIVERSITY OF TENNESSEE KNOXVILLE · PI BARRERA, FRANCISCO NICOLAS · 2016 to 2020
$1.7M
Sulfonylureas as repurposed agents against vulvovaginal candidiasisR21AI127942 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI PETERS, BRIAN M · 2018 to 2019
$418k
Targeted and forward genetic approaches to decipher the pathogenesis of symptomatic vulvovaginal candidiasisR21AI141829 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI PETERS, BRIAN M · 2019 to 2020
$418k
A novel role for the inflammasome in the immunopathogenesis of Candida vaginitisK22AI110541 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI PETERS, BRIAN M · 2016 to 2017
$268k
NIAID NIH HHS K22 AI110541NIAID NIH HHS R01 AI134796NIAID NIH HHS R21 AI127942NIAID NIH HHS R21 AI141829NIDCR NIH HHS R01 DE022550NIGMS NIH HHS R01 GM120642NIGMS NIH HHS T32 GM137793Wellcome TrustWellcome Trust 214229_Z_18Z
6 · The paper itself

Abstract

Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans, results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the ECE1 gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C. albicans isolates and whether this partly underlies differential pathogenicity observed clinically. Using a targeted sequencing approach, we determined that isolate 529L harbors a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin; this isoform was conserved amongst a collection of clinical isolates. Expression of the ECE1 open reading frame (ORF) from 529L in an SC5314-derived ece1Δ/Δ strain resulted in significantly reduced vaginopathogenicity as compared to an isogenic control expressing a wild-type (WT) ECE1 allele. However, in vitro challenge of vaginal epithelial cells with synthetic candidalysin demonstrated similar toxigenic activity amongst SC5314 and 529L isoforms. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed reduced secretion with the ORF from 529L that was associated with reduced virulence. A genetic survey of 78 clinical isolates demonstrated a conserved pattern between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein processing may contribute to differential pathogenicity amongst clinical isolates. Therefore, we present a new mechanism for attenuation of C. albicans virulence at the ECE1 locus.

Indexed as

AllelesAnimalsCandida albicansCandidiasis, VulvovaginalFemaleFungal ProteinsGenetic VariationHumansMiceVirulenceECE1 protein, Candida albicansFungal Proteins

Identifiers

PMID34506615
PMCPMC8432879
OpenAlexW3196544561

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.