The combined action of <I>ERG11</I> gene overexpression and its mutations in the development of <I>Candida albicans</I> resistance to triazolic antifungals
Introduction. Modern medicine is faced with the resistance of Candida spp. to antimycotics, due to changes in the expression and structure of the ERG11 gene, the molecular target of triazoles. These mechanisms often operate simultaneously, but the interaction between them remains poorly understood....
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | Russian |
| Published: |
Central Research Institute for Epidemiology
2025-07-01
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| Series: | Журнал микробиологии, эпидемиологии и иммунобиологии |
| Subjects: | |
| Online Access: | https://microbiol.crie.ru/jour/article/viewFile/18877/1610 |
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| Summary: | Introduction. Modern medicine is faced with the resistance of Candida spp. to antimycotics, due to changes in the expression and structure of the ERG11 gene, the molecular target of triazoles. These mechanisms often operate simultaneously, but the interaction between them remains poorly understood.
The aim of this study is to investigate the interaction between ERG11 gene overexpression and mutation in the development of triazole resistance in C. albicans.
Materials and methods. Eleven C. albicans strains from the G.N. Gabrichevsky Moscow Research Institute of Epidemiology culture collection were analyzed. Each strain was characterized by its ERG11 gene expression level, the presence of ERG11 mutations, and its susceptibility to the triazoles posaconazole, voriconazole, itraconazole and fluconazole.
Results. The C. albicans strains (n – number of tested strains) were categorized into four groups: Group 1 (n = 2, ERG11 overexpression only), Group 2 (n = 3, ERG11 mutations only), Group 3 (n = 4, both ERG11 overexpression and mutation) and Group 4 (n = 2, neither ERG11 overexpression nor mutation). The minimum inhibitory concentration (MIC) of Triazoles in Group 1 was 15.76-fold higher than in Group 2, 4.97-fold higher than in Group 3, and 2.51-fold lower than in Group 4 (p 0.05 for all comparisons). The MIC of triazoles in Group 2 was 3.17-fold lower than in Group 3 and 40.00-fold lower than in Group 4 (p 0.001). The MIC of triazoles in Group 3 was 12.5-fold lower than in Group 4 (p 0.001). Population-level variation in triazoles MIC was more strongly influenced by the isolated effect of ERG11 mutations (45.94%) than by the isolated effect of ERG11 overexpression (5.27-fold less).
Conclusion. Triazole resistance in C. albicans is influenced by the combined actions of ERG11 overexpression and mutation. ERG11 overexpression appears to contribute more to the absolute level of resistance, while ERG11 mutations have a greater impact on the diversity of resistance levels within the C. albicans population. |
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| ISSN: | 0372-9311 2686-7613 |