Penetration of Candida Biofilms by Antifungal Agents
Open accessAbstract
A filter disk assay was used to investigate the penetration of antifungal agents through biofilms containing single and mixed-species biofilms containing Candida. Fluconazole permeated all single-species Candida biofilms more rapidly than flucytosine. The rates of diffusion of either drug through biofilms of three strains of Candida albicans were similar. However, the rates of drug diffusion through biofilms of C. glabrata or C. krusei were faster than those through biofilms of C. parapsilosis or C. tropicalis. In all cases, after 3 to 6 h the drug concentration at the distal edge of the biofilm was very high (many times the MIC). Nevertheless, drug penetration failed to produce complete killing of biofilm cells. These results indicate that poor antifungal penetration is not a major drug resistance mechanism for Candida biofilms. The abilities of flucytosine, fluconazole, amphotericin B, and voriconazole to penetrate mixed-species biofilms containing C. albicans and Staphylococcus epidermidis (a slime-producing wild-type strain, RP62A, and a slime-negative mutant, M7) were also investigated. All four antifungal agents diffused very slowly through these mixed-species biofilms. In most cases, diffusion was slower with biofilms containing S. epidermidis RP62A, but amphotericin B penetrated biofilms containing the M7 mutant more slowly. However, the drug concentrations reaching the distal edges of the biofilms always substantially exceeded the MIC. Thus, although the presence of bacteria and bacterial matrix material undoubtedly retarded the diffusion of the antifungal agents, poor penetration does not account for the drug resistance of Candida biofilm cells, even in these mixed-species biofilms.
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In Candida species biofilms, carbohydrates, proteins, and nucleic acids form the extracellular matrix surrounding the cells.
“In Candida species biofilms, carbohydrates, proteins, and nucleic acids form the extracellular matrix that surround the cells in the biofilms [149,150,151,152,153,154].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [149]
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- Authors
- Al-Fattani, M. A., & Douglas, L. J.
- Affiliations
- University of Glasgow (GB)
- Corresponding author
- Douglas, L. Julia
- ORCID
- Douglas, L. Julia
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2004-09
- Volume
- 48
- Issue
- 9
- Pages
- 3291-3297
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC514766
- OpenAlex
- W2159297496
- Cited by
- 235
- References
- 44
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 5 · 2020: 6 · 2019: 12 · 2018: 8 · 2017: 21 · 2016: 12 · 2015: 11 · 2014: 20 · 2013: 12 · 2012: 9
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Update notices
- correction (2004-10-01)
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health – Kingdom of Saudi Arabia
- Pfizer UK
- 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 biofilms, drug diffusion, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, polymicrobial biofilms, Staphylococcus epidermidis, slime layer, fluconazole, 5-fluorocytosine, amphotericin B, voriconazole, antifungal resistance, minimum inhibitory concentration
- MeSH terms
- Amphotericin B, Antifungal Agents, Candida albicans, Culture Media, Diffusion, Flucytosine, Microscopy, Electron, Scanning, Mutation, Pyrimidines, Staphylococcus epidermidis, Triazoles, Colony Count, Microbial, Fluconazole, Biofilms, Voriconazole
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