CoChat
Sign Up
Cited by 164Antifungal resistance and susceptibilityFungal and yeast genetics researchLipid Membrane Structure and Behavior

Membrane Sphingolipid-Ergosterol Interactions Are Important Determinants of Multidrug Resistance in Candida albicans

Open access
Mukhopadhyay, Kasturi, Prasad, Tulika, Saini, Preeti, Pucadyil, Thomas J., Chattopadhyay, Amitabha, Prasad, Rajendra·2004·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.48.5.1778-1787.2004PMC PMC400589
Open this paper in CoChat — free account

Abstract

In this study, we examined the importance of membrane ergosterol and sphingolipids in the drug susceptibilities of Candida albicans . We used three independent methods to test the drug susceptibilities of erg mutant cells, which were defective in ergosterol biosynthesis. While spot and filter disk assays revealed that erg2 and erg16 mutant cells of C. albicans became hypersensitive to almost all of the drugs tested (i.e., 4-nitroquinoline oxide, terbinafine, o -phenanthroline, itraconazole, and ketoconazole), determination of the MIC at which 80% of the cells were inhibited revealed more than fourfold increase in susceptibility to ketoconazole and terbinafine. Treatment of wild-type C. albicans cells with fumonisin B1 resulted in 45% inhibition of sphingolipid biosynthesis and caused cells to become hypersensitive to the above drugs. Although erg mutants displayed enhanced membrane fluidity and passive diffusion, these changes alone were not sufficient to elicit the observed hypersusceptibility phenotype of erg mutants. For example, the induction in vitro of a 12% change in the membrane fluidity of C. albicans cells by a membrane fluidizer, benzyl alcohol, did not affect the drug susceptibilities of Candida cells. Additionally, the surface localization of green fluorescent protein-tagged Cdr1p, a major drug efflux pump protein of C. albicans , revealed that any disruption in ergosterol and sphingolipid interactions also interfered with its proper surface localization and functioning. A 50% reduction in the efflux of the Cdr1p substrate, rhodamine 6G, in erg mutant cells or in cells with a reduced sphingolipid content suggested a strong correlation between these membrane lipid components and this major efflux pump protein. Taken together, the results of our study demonstrate for the first time that there is an interaction between membrane ergosterol and sphingolipids, that a reduction in the content of either of these two components results in a disruption of this interaction, and that this disruption has deleterious effects on the drug susceptibilities of C. albicans cells.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1128/aac.48.5.1778-1787.2004

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ERG1, ERG7, ERG9, ERG25, ERG26, and ERG27 are essential, while ERG2, ERG3, ERG5, ERG6, and ERG24 are considered non-essential in ergosterol biosynthesis.

    “By using the technology of gene disruption and controlled gene expression, ERG1 , ERG7 , ERG9 , ERG25 , ERG26 , and ERG27 have been proved to be essential, while ERG2 , ERG3 , ERG5 , ERG6 , and ERG24 are considered to be non-essential in ergosterol biosynthesis.”

    From The synthesis, regulation, and functions of sterols in<i>Candida albicans</i>: Well-known but still lots to learn (2016) · cites this paper as [28]

    The Results (page unavailable) describe viable C. albicans erg2 mutants that grow without drugs, supporting the non-essential classification for ERG2. The paper does not establish the claimed essentiality of ERG1, ERG7, ERG9, ERG25, ERG26, or ERG27, or the non-essentiality of ERG3, ERG5, ERG6, or ERG24. It also does not report proving those classifications through gene disruption and controlled gene expression. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Odds F. C. 1988. Candida and candidosis: a review and bibliography. Ballière Tindall London England.

Cited by

Sorted by citations

Related

Authors
Mukhopadhyay, K., Prasad, T., Saini, P., Pucadyil, T. J., Chattopadhyay, A., & Prasad, R.
Affiliations
  • Jawaharlal Nehru University (IN)
  • Centre for Cellular and Molecular Biology (IN)
Corresponding author
Prasad, Rajendra
ORCID
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2004-05
Volume
48
Issue
5
Pages
1778-1787
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.48.5.1778-1787.2004
PMC
PMC400589
OpenAlex
W2157978054
Cited by
163
References
47
Citations by year
2026: 4 · 2025: 3 · 2024: 13 · 2023: 8 · 2022: 12 · 2021: 6 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 6 · 2016: 6 · 2015: 2 · 2014: 7 · 2013: 10 · 2012: 7
FWCI
4.94
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Council of Scientific and Industrial Research, India
  • International Centre for Genetic Engineering and Biotechnology
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 › Lipid Membrane Structure and Behavior
Keywords
Candida albicans, multidrug resistance, ergosterol, sphingolipids, membrane lipid interactions, ERG2, fumonisin B1, drug sensitivity, Cdr1p, drug efflux pumps, membrane fluidity, terbinafine, ketoconazole, itraconazole, 1,10-phenanthroline
MeSH terms
Antifungal Agents, Candida albicans, Culture Media, Ergosterol, Fungal Proteins, Luminescent Proteins, Membrane Lipids, Microbial Sensitivity Tests, Microscopy, Fluorescence, Spheroplasts, Sphingolipids, Fluorescence Polarization Immunoassay, Microscopy, Confocal, Drug Resistance, Multiple, Fungal, Membrane Transport Proteins, Green Fluorescent Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review