Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation In Vitro and In Vivo

Nobile, Clarissa J; Andes, David R; Nett, Jeniel E; Smith, Frank J; Yue, Fu; Phan, Quynh-Trang; Edwards, John E; Filler, Scott G; Mitchell, Aaron P

doi:10.1371/journal.ppat.0020063

Cited by 507Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation In Vitro and In Vivo

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Nobile, Clarissa J, Andes, David R, Nett, Jeniel E, Smith, Frank J, Yue, Fu, Phan, Quynh-Trang, Edwards, John E, Filler, Scott G +1 more·2006·PLoS Pathogens

DOI 10.1371/journal.ppat.0020063PMC PMC1487173

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Abstract

The fungal pathogen Candida albicans is frequently associated with catheter-based infections because of its ability to form resilient biofilms. Prior studies have shown that the transcription factor Bcr1 governs biofilm formation in an in vitro catheter model. However, the mechanistic role of the Bcr1 pathway and its relationship to biofilm formation in vivo are unknown. Our studies of biofilm formation in vitro indicate that the surface protein Als3, a known adhesin, is a key target under Bcr1 control. We show that an als3/als3 mutant is biofilm-defective in vitro, and that ALS3 overexpression rescues the biofilm defect of the bcr1/bcr1 mutant. We extend these findings with an in vivo venous catheter model. The bcr1/bcr1 mutant is unable to populate the catheter surface, though its virulence suggests that it has no growth defect in vivo. ALS3 overexpression rescues the bcr1/bcr1 biofilm defect in vivo, thus arguing that Als3 is a pivotal Bcr1 target in this setting. Surprisingly, the als3/als3 mutant forms a biofilm in vivo, and we suggest that additional Bcr1 targets compensate for the Als3 defect in vivo. Indeed, overexpression of Bcr1 targets ALS1, ECE1, and HWP1 partially restores biofilm formation in a bcr1/bcr1 mutant background in vitro, though these genes are not required for biofilm formation in vitro. Our findings demonstrate that the Bcr1 pathway functions in vivo to promote biofilm formation, and that Als3-mediated adherence is a fundamental property under Bcr1 control. Known adhesins Als1 and Hwp1 also contribute to biofilm formation, as does the novel protein Ece1.

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The biofilm master regulator Bcr1 and some of its downstream targets, including Als1, Als3, and Hwp1, are all required for adherence during biofilm formation.
“For example, the biofilm master regulator Bcr1 and some of its downstream targets, including the cell wall proteins Als1, Als3, and Hwp1, are all required for adherence during biofilm formation (23, 138, 141, 143, 145, 212).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [138]

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Authors: Nobile, C. J., Andes, D. R., Nett, J. E., Smith, F. J., Yue, F., Phan, Q.-T., Edwards, J. E., Filler, S. G., & Mitchell, A. P.
Affiliations: Columbia University (US)
University of Wisconsin–Madison (US)
University of California, Los Angeles (US)
Corresponding author: Mitchell, Aaron P
ORCID: Nobile, Clarissa J
Andes, David R
Nett, Jeniel E
Edwards, John E
Filler, Scott G
Mitchell, Aaron P
Venue: PLoS Pathogens
Publisher: Public Library of Science (PLoS)
Published: 2006-07-07
Volume: 2
Issue: 7
Pages: e63
ISSN: 1553-7366 (ISSN-L)
1553-7374
DOI: 10.1371/journal.ppat.0020063
PMC: PMC1487173
OpenAlex: W2002221873
Cited by: 507
References: 45
Citations by year: 2026: 12 · 2025: 18 · 2024: 19 · 2023: 20 · 2022: 25 · 2021: 32 · 2020: 20 · 2019: 29 · 2018: 24 · 2017: 30 · 2016: 26 · 2015: 26 · 2014: 29 · 2013: 34 · 2012: 33
FWCI: 14.66
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Pathogens (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship (California Digital Library) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: National Institutes of Health (NIH T32, HL07899)
National Heart, Lung, and Blood Institute (T32 HL07899, T32HL007899)
National Institute of Allergy and Infectious Diseases (R01AI019990, K08 AI01767, R01AI067703, R01-AI19990, K08AI001767, R01AI054928, R01AI057804)
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, ALS1, HWP1, endothelin-converting enzyme-1, catheter-related infection, fungal virulence, transcriptional regulation
MeSH terms: Animals, Candida albicans, Candidiasis, Catheterization, Cell Adhesion, Fungal Proteins, Genes, Fungal, Membrane Glycoproteins, Mice, Inbred BALB C, Mutation, Cell Adhesion Molecules, Gene Expression Regulation, Fungal, Rats, Sprague-Dawley, Biofilms, Mice, Rats, Proto-Oncogene Proteins c-bcr

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Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation In Vitro and In Vivo

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