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Cited by 165Antifungal resistance and susceptibilityBacterial biofilms and quorum sensingFungal and yeast genetics research

Role for Cell Density in Antifungal Drug Resistance in Candida albicans Biofilms

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Perumal, Palani, Mekala, Satish, Chaffin, W. LaJean·2007·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.01237-06PMC PMC1913227
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Abstract

Biofilms of Candida albicans are less susceptible to many antifungal drugs than are planktonic yeast cells. We investigated the contribution of cell density to biofilm phenotypic resistance. Planktonic yeast cells in RPMI 1640 were susceptible to azole-class drugs, amphotericin B, and caspofungin at 1 x 10(3) cells/ml (standard conditions) using the XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt] assay. As reported by others, as the cell concentration increased to 1 x 10(8) cells/ml, resistance was observed with 10- to 20-fold-greater MICs. Biofilms that formed in microtiter plate wells, like high-density planktonic organisms, were resistant to drugs. When biofilms were resuspended before testing, phenotypic resistance remained, but organisms, when diluted to 1 x 10(3) cells/ml, were susceptible. Drug-containing medium recovered from high-cell-density tests inhibited low-cell-density organisms. A fluconazole-resistant strain showed greater resistance at high planktonic cell density, in biofilm, and in resuspended biofilm than did low-density planktonic or biofilm organisms. A strain lacking drug efflux pumps CDR1, CDR2, and MDR1, while susceptible at a low azole concentration, was resistant at high cell density and in biofilm. A strain lacking CHK1 that fails to respond to the quorum-sensing molecule farnesol had the same response as did the wild type. FK506, reported to abrogate tolerance to azole drugs at low cell density, had no effect on tolerance at high cell density and in biofilm. These observations suggested that cell density has a role in the phenotypic resistance of biofilm, that neither the drug efflux pumps tested nor quorum sensing through Chk1p contributes to resistance, and that azole drug tolerance at high cell density differs mechanistically from tolerance at low cell density.

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Crossref · 10.1128/aac.01237-06

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  • Increasing cell concentration in drug resistance assays increases resistance specifically to fluconazole, ketoconazole, amphotericin B, and caspofungin up to twenty-fold.

    “Indeed, if this cell concentration is augmented in the drug resistance assays, resistance specifically to fluconazole, ketoconazole, amphotericin B, and caspofungin is increased up to twenty-fold [147].”

    From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [147]

  • Inoculum size can affect susceptibility results.

    “It is well recognized that the inoculum size can affect susceptibility results [130,144,145,146,147].”

    From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [147]

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Authors
Perumal, P., Mekala, S., & Chaffin, W. L.
Affiliations
Texas Tech University Health Sciences Center (US)
ORCID
Perumal, Palani
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2007-07
Volume
51
Issue
7
Pages
2454-2463
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.01237-06
PMC
PMC1913227
OpenAlex
W2134721427
Cited by
165
References
65
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 14 · 2016: 12 · 2015: 10 · 2014: 11 · 2013: 11 · 2012: 13
FWCI
7.18
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Dental and Craniofacial Research (1R01 DE 14029, R01DE014029)
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, antifungal resistance, cell density, fluconazole resistance, quorum sensing, farnesol, Chk1, CDR1, CDR2, MDR1, efflux pumps, FK506, caspofungin, amphotericin B
MeSH terms
Amphotericin B, Antifungal Agents, Candida albicans, Fungal Proteins, Microbial Sensitivity Tests, Fluconazole, Biofilms, Drug Resistance, Fungal

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