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Cited by 109Antifungal resistance and susceptibilityFungal and yeast genetics researchYeasts and Rust Fungi Studies

Reduced Susceptibility to Polyenes Associated with a Missense Mutation in the ERG6 Gene in a Clinical Isolate of Candida glabrata with Pseudohyphal Growth

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Vandeputte, Patrick, Tronchin, Guy, Bergès, Thierry, Hennequin, Christophe, Chabasse, Dominique, Bouchara, Jean-Philippe·2007·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.01510-06PMC PMC1803144
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Abstract

Little information is available about the molecular mechanisms responsible for polyene resistance in pathogenic yeasts. A clinical isolate of Candida glabrata with a poor susceptibility to polyenes, as determined by disk diffusion method and confirmed by determination of MIC, was recovered from a patient treated with amphotericin B. Quantitative analysis of sterols revealed a lack of ergosterol and an accumulation of late sterol intermediates, suggesting a defect in the final steps of the ergosterol pathway. Sequencing of CgERG11, CgERG6, CgERG5, and CgERG4 genes revealed exclusively a unique missense mutation in CgERG6 leading to the substitution of a cysteine by a phenylalanine in the corresponding protein. In addition, real-time reverse transcription-PCR demonstrated an overexpression of genes encoding enzymes involved in late steps of the ergosterol pathway. Moreover, this isolate exhibited a pseudohyphal growth whatever the culture medium used, and ultrastructural changes of the cell wall of blastoconidia were seen consisting in a thinner inner layer. Cell wall alterations were also suggested by the higher susceptibility of growing cells to Calcofluor white. Additionally, complementation of this isolate with a wild-type copy of the CgERG6 gene restored susceptibility to polyenes and a classical morphology. Together, these results demonstrated that mutation in the CgERG6 gene may lead to a reduced susceptibility to polyenes and to a pseudohyphal growth due to the subsequent changes in sterol content of the plasma membrane.

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Crossref · 10.1128/aac.01510-06

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  • In another clinical isolate of Candida glabrata recovered from a patient treated with amphotericin B and with poor susceptibility to polyenes, a deficiency of ergosterol and an accumulation of late sterol intermediates was detected.

    “In another clinical isolate of C. glabrata recovered from a patient treated with amphotericin B and with a poor susceptibility to polyenes, a deficiency of ergosterol and an accumulation of late sterol intermediates was detected”

    From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [116]

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Authors
Vandeputte, P., Tronchin, G., Bergès, T., Hennequin, C., Chabasse, D., & Bouchara, J.-P.
Affiliations
  • Centre Hospitalier Universitaire d'Angers (FR)
  • Laboratoire de Génétique de la Levure, CNRS UMR 6161, Faculté des Sciences, 86022 Poitiers Cedex
  • Hôpital Tenon (FR)
Corresponding author
Vandeputte, Patrick
ORCID
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2007-03
Volume
51
Issue
3
Pages
982-990
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.01510-06
PMC
PMC1803144
OpenAlex
W2122550330
Cited by
109
References
44
Citations by year
2026: 2 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 11 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 5
FWCI
3.30
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)
  • HAL (submittedVersion)
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 › Yeasts and Rust Fungi Studies
Keywords
Candida glabrata, polyene resistance, missense mutations, ergosterol biosynthesis, sterol intermediates, pseudohyphal growth, cell wall ultrastructure, amphotericin B, gene complementation, antifungal resistance
MeSH terms
Antifungal Agents, Candidiasis, Genes, Fungal, Genetic Complementation Test, Methyltransferases, Microbial Sensitivity Tests, Molecular Sequence Data, Phenotype, Polyenes, RNA, Fungal, RNA, Messenger, Sterols, DNA Primers, Mutation, Missense, Reverse Transcriptase Polymerase Chain Reaction, Candida glabrata

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