A Small Subpopulation of Blastospores in Candida albicans Biofilms Exhibit Resistance to Amphotericin B Associated with Differential Regulation of Ergosterol and β -1,6-Glucan Pathway Genes

Khot, Prasanna D.; Suci, Peter A.; Miller, R. Lance; Nelson, Raoul D.; Tyler, Bonnie J.

doi:10.1128/aac.00997-06

Cited by 104Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

A Small Subpopulation of Blastospores in Candida albicans Biofilms Exhibit Resistance to Amphotericin B Associated with Differential Regulation of Ergosterol and β -1,6-Glucan Pathway Genes

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Khot, Prasanna D., Suci, Peter A., Miller, R. Lance, Nelson, Raoul D., Tyler, Bonnie J.·2006·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.00997-06PMC PMC1635220

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Abstract

The resistance of Candida albicans biofilms to a broad spectrum of antimicrobial agents has been well documented. Biofilms are known to be heterogeneous, consisting of microenvironments that may induce formation of resistant subpopulations. In this study we characterized one such subpopulation. C. albicans biofilms were cultured in a tubular flow cell (TF) for 36 h. The relatively large shear forces imposed by draining the TF removed most of the biofilm, which consisted of a tangled mass of filamentous forms with associated clusters of yeast forms. This portion of the biofilm exhibited the classic architecture and morphological heterogeneity of a C. albicans biofilm and was only slightly more resistant than either exponential- or stationary-phase planktonic cells. A submonolayer fraction of blastospores that remained on the substratum was resistant to 10 times the amphotericin B dose that eliminated the activity of the planktonic populations. A comparison between planktonic and biofilm populations of transcript abundance for genes coding for enzymes in the ergosterol ( ERG1 , - 3 , - 5 , - 6 , - 9 , - 11 , and - 25 ) and β-1,6-glucan ( SKN and KRE1 , - 5 , - 6 , and - 9 ) pathways was performed by quantitative RT-PCR. The results indicate a possible association between the high level of resistance exhibited by the blastospore subpopulation and differential regulation of ERG1 , ERG25 , SKN1 , and KRE1 . We hypothesize that the resistance originates from a synergistic effect involving changes in both the cell membrane and the cell wall.

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Yeast persister cells were first discovered as a small population in C. albicans biofilms.
“Yeast persister cells were first discovered as a small population in C. albicans biofilms [165,166].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [165]
The drug resistance of persister cells is independent of cell membrane composition and efflux pump expression; rather, it is the result of the metabolically dormant state of the cells.
“Although we know little about the formation and roles of persister cells in C. albicans biofilms, we do know that the drug resistance of persister cells is independent of cell membrane composition and efflux pump expression; rather, it is the result of the metabolically dormant state of the cells (88, 100).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [88]

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A small subpopulation of blastospores in Candida albicans biofilms exhibit resistance to amphotericin B associated with differential regulation of ergosterol and ß-1,6-glucan pathway genes
Khot, P. D., Suci, P. A., Miller, R. L., Nelson, R. D., & Tyler, B. J. (2006) · Montana State University ScholarWorks (Montana State University)
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Transcriptional response to fluconazole and amphotericin B in Candida albicans biofilms
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Authors: Khot, P. D., Suci, P. A., Miller, R. L., Nelson, R. D., & Tyler, B. J.
Affiliations: University of Utah (US)
Montana State University (US)
ORCID: Tyler, Bonnie J.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2006-11
Volume: 50
Issue: 11
Pages: 3708-3716
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.00997-06
PMC: PMC1635220
OpenAlex: W2168849172
Cited by: 104
References: 78
Citations by year: 2025: 3 · 2024: 5 · 2023: 5 · 2022: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 12 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 4 · 2012: 6
FWCI: 4.32
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (R01GM079554, 1 R21 GM 079554)
National Institute of Dental and Craniofacial Research (R01DE013231, DE13231-02)
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, blastospores, amphotericin B resistance, subgroup heterogeneity, ergosterol biosynthesis, ERG1, plasma membrane, cell wall, mRNA levels
MeSH terms: Amphotericin B, Antifungal Agents, Candida albicans, DNA, Fungal, Ergosterol, Genes, Fungal, Microbial Sensitivity Tests, Microscopy, Electron, Scanning, RNA, Fungal, Spores, Fungal, Transcription, Genetic, DNA Primers, DNA, Complementary, Biofilms, Reverse Transcriptase Polymerase Chain Reaction, Drug Resistance, Fungal, beta-Glucans

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A Small Subpopulation of Blastospores in Candida albicans Biofilms Exhibit Resistance to Amphotericin B Associated with Differential Regulation of Ergosterol and β -1,6-Glucan Pathway Genes

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