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Cited by 59Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

Targeted Changes of the Cell Wall Proteome Influence Candida albicans Ability to Form Single- and Multi-strain Biofilms

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Cabral, Vitor, Znaidi, Sadri, Walker, Louise A., Martin-Yken, Hélène, Dague, Etienne, Legrand, Mélanie, Lee, Keunsook, Chauvel, Murielle +6 more·2014·PLoS Pathogens
DOI 10.1371/journal.ppat.1004542PMC PMC4263760
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Abstract

Biofilm formation is an important virulence trait of the pathogenic yeast Candida albicans. We have combined gene overexpression, strain barcoding and microarray profiling to screen a library of 531 C. albicans conditional overexpression strains (∼10% of the genome) for genes affecting biofilm development in mixed-population experiments. The overexpression of 16 genes increased strain occupancy within a multi-strain biofilm, whereas overexpression of 4 genes decreased it. The set of 16 genes was significantly enriched for those encoding predicted glycosylphosphatidylinositol (GPI)-modified proteins, namely Ihd1/Pga36, Phr2, Pga15, Pga19, Pga22, Pga32, Pga37, Pga42 and Pga59; eight of which have been classified as pathogen-specific. Validation experiments using either individually- or competitively-grown overexpression strains revealed that the contribution of these genes to biofilm formation was variable and stage-specific. Deeper functional analysis of PGA59 and PGA22 at a single-cell resolution using atomic force microscopy showed that overexpression of either gene increased C. albicans ability to adhere to an abiotic substrate. However, unlike PGA59, PGA22 overexpression led to cell cluster formation that resulted in increased sensitivity to shear forces and decreased ability to form a single-strain biofilm. Within the multi-strain environment provided by the PGA22-non overexpressing cells, PGA22-overexpressing cells were protected from shear forces and fitter for biofilm development. Ultrastructural analysis, genome-wide transcript profiling and phenotypic analyses in a heterologous context suggested that PGA22 affects cell adherence through alteration of cell wall structure and/or function. Taken together, our findings reveal that several novel predicted GPI-modified proteins contribute to the cooperative behaviour between biofilm cells and are important participants during C. albicans biofilm formation. Moreover, they illustrate the power of using signature tagging in conjunction with gene overexpression for the identification of novel genes involved in processes pertaining to C. albicans virulence.

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  • The ectopic overexpression or deletion of other PGA family proteins affects fungal adhesion as well as CSP sensitivity.

    “Interestingly, the ectopic overexpression or deletion of other PGA family proteins affects fungal adhesion as well as CSP sensitivity (45, 54), and PGA6 was found to be upregulated in CSP-treated C. auris cells (55).”

    From Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris (2022) · cites this paper as [54]

    The Discussion reports that both overexpression and deletion of PGA22 increase adherence in C. albicans under the conditions tested. The Results also link PGA22 and PGA59 overexpression to adhesion. Our copy does not report that these changes affect CSP sensitivity, so it supports only the adhesion part of the claim. (LLM, conf=0.88)

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References 75 · Cited by 59

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Authors
Cabral, V., Znaidi, S., Walker, L. A., Martin-Yken, H., Dague, E., Legrand, M., Lee, K., Chauvel, M., Firon, A., Rossignol, T., Richard, M. L., Munro, C. A., Bachellier-Bassi, S., & d'Enfert, C.
Affiliations
  • Institut Pasteur (FR)
  • University of Aberdeen (GB)
  • AgroParisTech (FR)
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2014-12-11
Volume
10
Issue
12
Pages
e1004542
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1004542
PMC
PMC4263760
OpenAlex
W2068826765
Cited by
59
References
75
Citations by year
2025: 4 · 2024: 5 · 2023: 4 · 2022: 11 · 2021: 8 · 2020: 2 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 5 · 2015: 5
FWCI
3.52
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Wellcome Trust (214004, WT088858MA)
  • European Commission (LSHM-CT-2005-518199, 214004)
  • University of Aberdeen
  • Agence Nationale de la Recherche (ANR-08-MIE-033-01, 30024331, ANR-08-MIEN-0033, ANR-11-JSV5-0001)
  • Medical Research Council (G0400284)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords
Candida albicans, biofilm formation, cell wall proteome, cell adhesion, cell clustering, virulence genes, cooperative behavior, cell wall ultrastructure
MeSH terms
Candida albicans, Cell Adhesion, Cell Wall, Fungal Proteins, Phenotype, Gene Expression Regulation, Fungal, Biofilms, Proteome, Shear Strength, Transcriptome

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