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Biofilm Formation by the Fungal Pathogen Candida albicans : Development, Architecture, and Drug Resistance
Open accessAbstract
Biofilms are a protected niche for microorganisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm models formed on bioprosthetic materials, we demonstrated that biofilm formation proceeds through three distinct developmental phases. These growth phases transform adherent blastospores to well-defined cellular communities encased in a polysaccharide matrix. Fluorescence and confocal scanning laser microscopy revealed that C. albicans biofilms have a highly heterogeneous architecture composed of cellular and noncellular elements. In both models, antifungal resistance of biofilm-grown cells increased in conjunction with biofilm formation. The expression of agglutinin-like ( ALS ) genes, which encode a family of proteins implicated in adhesion to host surfaces, was differentially regulated between planktonic and biofilm-grown cells. The ability of C. albicans to form biofilms contrasts sharply with that of Saccharomyces cerevisiae , which adhered to bioprosthetic surfaces but failed to form a mature biofilm. The studies described here form the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance and provide the means to design novel therapies for biofilm-based infections.
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In the citing paper
“Sterol analyses show that ergosterol levels are signi fi cantly decreased in both intermediate (12-30h) and mature phases (31-72h), compared to those in earlyphase (0-11h) bio fi lms, and this is connected to the decreased expression of ergosterol biosynthetic genes ( ERG25 , ERG11 , and ERG6 ).”
From The synthesis, regulation, and functions of sterols in Candida albicans: Well-known but still lots to learn (2016) · cites this paper as [74]
Experimental — accuracy not yet measuredIn the citing paper
“Moreover, this yeast can easily colonize implanted medical devices thanks to its capacity to form stable biofilms, a contamination that could lead to bloodstream infections and even invasive systemic infections of organs or tissues [83].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [83]
In the citing paper
“The MICbiofilm of SM21 increases as the biofilm matures, a common phenomenon among antifungal agents [53].”
From In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections (2014) · cites this paper as [53]
In the citing paper
“Specific biofilm formation genes are being brought up regarding different roles in biofilm resistance: peroxisomal catalase (CTA1), the biosynthesis and degradation of tyrosine genes (ARO), the muscle creatine kinase (MSK), the heat shock protein 90 (HSP 90), the sphingolipid biosynthesis (SKN 1 and KRE1), SIR, RIF, and, finally, the extracellular matrix (ECM) regulators: zinc regulated genes (ZAP”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [159]
In the citing paper
“A study showed that the resistance to chlorhexidine, fluconazole, amphotericin B, and nystatin increased as biofilms mature over time, corresponding to a growth in metabolic activity over biofilm maturation.”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [159]
In the citing paper
“However, in these experiments, cell number was not controlled, thus making it unclear if this is a true demonstration of metabolic activity [159].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [159]
In the citing paper
“C. albicans produces highly structured biofilms composed of multiple cell types (i.e., round, budding yeast-form cells; oval pseudohyphal cells; and elongated, cylindrical hyphal cells) encased in an extracellular matrix (23, 61, 158, 161).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [23]
In the citing paper
“C. albicans biofilm formation comprises four temporal stages (10, 23, 47, 75, 142, 194) (Figure 1): (a) adherence to a surface (spherical yeast cells), (b) proliferation to form a basal layer of anchoring cells, (c) growth of pseudohyphae (ellipsoid cells joined end to end) and hyphae (chains of cylindrical cells) concomitant with production of extracellular matrix material, and (d) slow dispersal”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [23]
In the citing paper
“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 [23]
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Metadata
- Authors
- Chandra, J., Kuhn, D. M., Mukherjee, P. K., Hoyer, L. L., McCormick, T., & Ghannoum, M. A.
- Affiliations
- University Hospitals of Cleveland (US)
- University of Illinois Urbana-Champaign (US)
- Case Western Reserve University (US)
- ORCID
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2001-09-15
- Volume
- 183
- Issue
- 18
- Pages
- 5385-5394
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC95423
- OpenAlex
- W2125848302
- Cited by
- 1,578
- References
- 51
- Citations by year
- 2026: 36 · 2025: 48 · 2024: 48 · 2023: 71 · 2022: 68 · 2021: 88 · 2020: 77 · 2019: 84 · 2018: 73 · 2017: 94 · 2016: 89 · 2015: 81 · 2014: 102 · 2013: 78 · 2012: 83
- FWCI
- 16.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI035097, AI36219, AI35097-03, AIO7024, P30AI036219)
- National Institute of Dental and Craniofacial Research (R01-DE13992, R01DE013992)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida albicans, biofilm formation, antifungal resistance, biofilm structure, planktonic versus biofilm growth, fungal adhesion, Saccharomyces cerevisiae comparison
- MeSH terms
- Antifungal Agents, Candida albicans, Candidiasis, Drug Resistance, Microbial, Fungal Proteins, Humans, Microbial Sensitivity Tests, Silicones, Gene Expression Regulation, Fungal, Biofilms, Microscopy, Confocal, Polymethyl Methacrylate
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