Evidence map›Paper›PMID 31116789›Full record

ArticlePLoS pathogens2019

Circuit diversification in a biofilm regulatory network.

Manning Y Huang, Carol A Woolford, Gemma May, C Joel McManus, Aaron P Mitchell

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. 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 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

87 citing papers in PubMed, 111 citations in OpenAlex.

  1. Two Ume6 target gene classes in the biofilm regulatory network ofbioRxiv : the preprint server for biology · 2026
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  9. A roadmap to chemically reactive species: how diverse oxidants affectMicrobiology and molecular biology reviews : MMBR · 2025
    Review
  10. Hgt17-Adr1 Relationship inJournal of fungi (Basel, Switzerland) · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Fungal biofilms in human health and disease.Nature reviews. Microbiology · 2025
    Review
  15. Article
  16. Roles of P-body factors inbioRxiv : the preprint server for biology · 2025
    Article
  17. Evaluation of biofilm formation and antimicrobial susceptibility (drug resistance) of Candida albicans isolates.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025
    Article
  18. Article
  19. Article
  20. Strain variation inmSphere · 2024
    Article

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Manning Y HuangDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States of America.ORCID 0000-0001-6045-9698
Carol A WoolfordDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States of America.ORCID 0000-0001-6261-3468
Gemma MayDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States of America.
C Joel McManusDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States of America.ORCID 0000-0002-6605-2642
Aaron P MitchellDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States of America.ORCID 0000-0002-0868-4000
Carnegie Mellon University · US

Funding

GENETIC MANIPULATION OF DIVERSE CANDIDA ALBICANS ISOLATESR21AI135178 · NIAID · CARNEGIE-MELLON UNIVERSITY · PI MITCHELL, AARON P · 2018 to 2019
$418k
NIAID NIH HHS R21 AI135178
6 · The paper itself

Abstract

Genotype-phenotype relationships can vary extensively among members of a species. One cause of this variation is circuit diversification, the alteration of gene regulatory relationships among members of a species. Circuit diversification is thought to be a starting point for the circuit divergence or rewiring that occurs during speciation. How widespread is circuit diversification? Here we address this question with the fungal pathogen Candida albicans, which forms biofilms rich in distinctive hyphal cells as a prelude to infection. Our understanding of the biofilm/hyphal regulatory network comes primarily from studies of one clinical isolate, strain SC5314, and its marked derivatives. We used CRISPR-based methods to create mutations of four key biofilm transcription factor genes-BCR1, UME6, BRG1, and EFG1 -in SC5314 and four additional clinical isolates. Phenotypic analysis revealed that mutations in BCR1 or UME6 have variable impact across strains, while mutations in BRG1 or EFG1 had uniformly severe impact. Gene expression, sampled with Nanostring probes and examined comprehensively for EFG1 via RNA-Seq, indicates that regulatory relationships are highly variable among isolates. Our results suggest that genotype-phenotype relationships vary in this strain panel in part because of differences in control of BRG1 by BCR1, a hypothesis that is supported through engineered constitutive expression of BRG1. Overall, the data show that circuit diversification is the rule, not the exception, in this biofilm/hyphal regulatory network.

Indexed as

Gene Expression Regulation, FungalBiofilmsCandida albicansCandidiasisFungal ProteinsGenetic Association StudiesGenetic SpeciationHumansHyphaeSignal TransductionTranscription FactorsFungal ProteinsTranscription Factors

Identifiers

PMID31116789
PMCPMC6530872
OpenAlexW2944959421

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.