Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature

Morio, Florent; Loge, Cedric; Besse, Bernard; Hennequin, Christophe; Le Pape, Patrice

doi:10.1016/j.diagmicrobio.2009.11.006

Cited by 279Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature

Morio, Florent, Loge, Cedric, Besse, Bernard, Hennequin, Christophe, Le Pape, Patrice·2010·Diagnostic Microbiology and Infectious Disease

DOI 10.1016/j.diagmicrobio.2009.11.006

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Abstract

For several years, azole antifungal drugs have been a treatment option for potentially life-threatening Candida infections. However, azole resistance can occur through various mechanisms such as alterations in ERG11, encoding lanosterol 14alpha-demethylase (CYP51). In this study, we investigated the antifungal susceptibility to fluconazole, itraconazole, and voriconazole of 73 clinical isolates of Candida albicans. Screening for amino acid substitutions in Erg11 was performed on each of the 73 isolates. Twenty isolates displayed a marked decrease in azole susceptibility. Amino acid substitutions were detected in more than two-thirds of the strains. In all, 23 distinct substitutions were identified. Four have not been described previously, among which N136Y and Y447H are suspected to be involved in azole resistance. We suggest that the high genetic polymorphism of ERG11 must be considered in the rationale design of new azole compounds targeting lanosterol 14alpha-demethylase. A review of all Erg11 amino acid polymorphisms described to date is given.

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In clinical isolates of C. albicans, over 140 distinct Erg11 amino acid substitutions have been reported, with most clustering into three hot spot regions.
“In clinical isolates of C. albicans, over 140 distinct Erg11 amino acid substitutions have been reported in the literature, with most clustering into three hot spot regions9,10.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [9]
As azole antifungals emerged as a common first-line option, documentation of new ERG11 mutations in azole-resistant clinical isolates continued to appear, though not all documented mutations were definitively shown to be tied to azole resistance.
“As the azole antifungals emerged as a common first-line option in the treatment of many superficial and invasive fungal infections, documentation of new ERG11 mutations in azole-resistant clinical isolates continued to appear, though not all documented mutations were definitively shown to be tied to azole resistance.124–137”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans (2020) · cites this paper as [130]

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Authors: Morio, F., Loge, C., Besse, B., Hennequin, C., & Le Pape, P.
Affiliations: Centre Hospitalier Universitaire de Nantes (FR)
Assistance Publique – Hôpitaux de Paris (FR)
ORCID: Morio, Florent
Hennequin, Christophe
Venue: Diagnostic Microbiology and Infectious Disease
Publisher: Elsevier BV
Published: 2010-04
Volume: 66
Issue: 4
Pages: 373-384
ISSN: 0732-8893 (ISSN-L)
DOI: 10.1016/j.diagmicrobio.2009.11.006
OpenAlex: W2112936110
Cited by: 279
References: 45
Citations by year: 2026: 10 · 2025: 13 · 2024: 9 · 2023: 23 · 2022: 19 · 2021: 17 · 2020: 22 · 2019: 27 · 2018: 16 · 2017: 21 · 2016: 17 · 2015: 15 · 2014: 24 · 2013: 17 · 2012: 12
FWCI: 9.43
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Diagnostic Microbiology and Infectious Disease (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: Université de Nantes
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Candida albicans, azole resistance, ERG11, lanosterol 14α-demethylase, CYP51, amino acid substitutions, fluconazole, itraconazole, voriconazole, antifungal susceptibility, clinical isolates, genetic polymorphism
MeSH terms: Antifungal Agents, Candida albicans, Candidiasis, Cytochrome P-450 Enzyme System, DNA, Fungal, Fungal Proteins, Humans, Microbial Sensitivity Tests, Molecular Sequence Data, Pyrimidines, Triazoles, Fluconazole, Sequence Analysis, DNA, Itraconazole, Amino Acid Substitution, Mutation, Missense, Drug Resistance, Fungal, Sterol 14-Demethylase, Voriconazole

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Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature

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