Cited by 170Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

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Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation

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Nett, Jeniel E., Sanchez, Hiram, Cain, Michael T., Ross, Kelly M., Andes, David R.·2011·Eukaryotic Cell

DOI 10.1128/ec.05126-11PMC PMC3232725

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Abstract

Candida albicans frequently infects medical devices by growing as a biofilm, i.e., a community of adherent organisms entrenched in an extracellular matrix. During biofilm growth, Candida spp. acquire the ability to resist high concentrations of antifungal drugs. One recently recognized biofilm resistance mechanism involves drug sequestration by matrix β-1,3 glucan. Using a candidate gene approach, we investigated potential C. albicans β-1,3-glucan regulators, based on their homology to Saccharomyces cerevisiae , including SMI1 and protein kinase C (PKC) pathway components. We identified a role for the SMI1 in biofilm matrix glucan production and development of the associated drug resistance phenotype. This pathway appears to act through transcription factor Rlmp and glucan synthase Fks1p. The phenotypes of these mutant biofilms mimicked those of the smi1 Δ/ smi1 Δ biofilm, and overexpression of FKS1 in the smi1 Δ/ smi1 Δ mutant restored the biofilm resistant phenotype. However, control of this pathway is distinct from that of the upstream PKC pathway because the pkc1 Δ/ pkc1 Δ, bck1 Δ/ bck1 Δ, mkk2 Δ/ mkk2 Δ, and mkc1 Δ/ mkc1 Δ biofilms retained the resistant phenotype of the parent strain. In addition, resistance to cell-perturbing agents and gene expression data do not support a significant role for the cell wall integrity pathway during the biofilm formation. Here we show that Smi1p functions in conjunction with Rlm1p and Fks1p to produce drug-sequestering biofilm β-glucan. Our work provides new insight into how the C. albicans biofilm matrix production and drug resistance pathways intersect with the planktonic cell wall integrity pathway. This novel connection helps explain how pathogens in a multicellular biofilm community are protected from anti-infective therapy.

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Authors: Nett, J. E., Sanchez, H., Cain, M. T., Ross, K. M., & Andes, D. R.
Affiliations: University of Wisconsin–Madison (US)
Department of Medicine, University of Wisconsin, Madison, Wisconsin
Corresponding author: Andes, David R.
ORCID: Nett, Jeniel E.
Cain, Michael T.
Andes, David R.
Venue: Eukaryotic Cell
Publisher: American Society for Microbiology
Published: 2011-12
Volume: 10
Issue: 12
Pages: 1660-1669
ISSN: 1535-9778 (ISSN-L)
1535-9786
DOI: 10.1128/ec.05126-11
PMC: PMC3232725
OpenAlex: W2138246367
Cited by: 168
References: 54
Citations by year: 2026: 6 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 13 · 2017: 12 · 2016: 17 · 2015: 12 · 2014: 9 · 2013: 17 · 2012: 7
FWCI: 7.33
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Eukaryotic Cell (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (T32HL007899)
National Institute of Allergy and Infectious Diseases (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, antifungal resistance, β-1,3-glucan, extracellular matrix, glucan synthase, protein kinase C pathway, cell wall integrity pathway, drug sequestration, medical device infections, biofilm formation
MeSH terms: Animals, Antifungal Agents, Candida albicans, Candidiasis, Cell Wall, Fungal Proteins, Glucosyltransferases, Protein Kinase C, Virulence, Fluconazole, Gene Expression Regulation, Fungal, Biofilms, Drug Resistance, Fungal, beta-Glucans, Mice, Rats, Gene Knockout Techniques, Catheters

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Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation

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