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A Candida Biofilm-Induced Pathway for Matrix Glucan Delivery: Implications for Drug Resistance
Open accessAbstract
Extracellular polysaccharides are key constituents of the biofilm matrix of many microorganisms. One critical carbohydrate component of Candida albicans biofilms, β-1,3 glucan, has been linked to biofilm protection from antifungal agents. In this study, we identify three glucan modification enzymes that function to deliver glucan from the cell to the extracellular matrix. These enzymes include two predicted glucan transferases and an exo-glucanase, encoded by BGL2, PHR1, and XOG1, respectively. We show that the enzymes are crucial for both delivery of β-1,3 glucan to the biofilm matrix and for accumulation of mature matrix biomass. The enzymes do not appear to impact cell wall glucan content of biofilm cells, nor are they necessary for filamentation or biofilm formation. We demonstrate that mutants lacking these genes exhibit enhanced susceptibility to the commonly used antifungal, fluconazole, during biofilm growth only. Transcriptional analysis and biofilm phenotypes of strains with multiple mutations suggest that these enzymes act in a complementary fashion to distribute matrix downstream of the primary β-1,3 glucan synthase encoded by FKS1. Furthermore, our observations suggest that this matrix delivery pathway works independently from the C. albicans ZAP1 matrix formation regulatory pathway. These glucan modification enzymes appear to play a biofilm-specific role in mediating the delivery and organization of mature biofilm matrix. We propose that the discovery of inhibitors for these enzymes would provide promising anti-biofilm therapeutics.
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In the citing paper
“This complex has been linked to the antifungal resistance biofilm phenotype via sequestration of antifungal (20, 22).”
From Dual function of Candida auris mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host (2025) · cites this paper as [22]
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“the biofilm matrix glucan has demonstrated the ability to bind and sequester antifungal drugs, including fluconazole, preventing them from acting intracellularly.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [179]
In the citing paper
“Finally, Taff et al. [110] identified two glucan transferases and an exo-glucanase that deliver glucan from the cell to the extracellular matrix, playing a biofilm-specific role, by mediating the distribution and organization of mature biofilm matrix.”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [110]
In the citing paper
“Genes involved in production and delivery of β-1,3-glucans include the synthase-encoding gene FKS1 and the genes BGL2, XOG1, and PHR1, which encode proteins involved in the modification and transport of β-glucans (132, 189).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [189]
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Self-citation
Metadata
- Authors
- Taff, H. T., Nett, J. E., Zarnowski, R., Ross, K. M., Sanchez, H., Cain, M. T., Hamaker, J., Mitchell, A. P., & Andes, D. R.
- Affiliations
- University of Wisconsin–Madison (US)
- Columbia University (US)
- Carnegie Mellon University (US)
- Corresponding author
- Andes, David R.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-08-02
- Volume
- 8
- Issue
- 8
- Pages
- e1002848
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC3410897
- OpenAlex
- W2124380402
- Cited by
- 291
- References
- 59
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 13 · 2023: 31 · 2022: 21 · 2021: 16 · 2020: 18 · 2019: 16 · 2018: 15 · 2017: 21 · 2016: 32 · 2015: 28 · 2014: 20 · 2013: 21 · 2012: 2
- FWCI
- 14.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH-R01)
- National Heart, Lung, and Blood Institute (T32HL007899)
- National Institute of General Medical Sciences (T32GM008692)
- National Institute of Allergy and Infectious Diseases (R01AI067703, R01AI073289)
- 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 matrix, β-1,3-glucan, BGL2, PHR1, FKS1, fluconazole susceptibility, antifungal resistance, exopolysaccharides, biofilm formation, Zap1
- MeSH terms
- Animals, Candida albicans, Candidiasis, Fungal Proteins, Glucans, Glucosyltransferases, Membrane Glycoproteins, Mutation, Biofilms, Drug Resistance, Fungal, Rats
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