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. 2024 Feb 27:17:769-777.
doi: 10.2147/IDR.S431024. eCollection 2024.

Roles of Nucleolar Factor RCL1 in Itraconazole Resistance of Clinical Candida albicans Under Different Stress Conditions

Jing Yang  1 , Yan Ma  1 , Bo Li  1 , Zhiqin Xi  1 , Li Zhang  1 , Yuxi Wang  1 , Wenli Feng  1
Affiliations

Roles of Nucleolar Factor RCL1 in Itraconazole Resistance of Clinical Candida albicans Under Different Stress Conditions

Jing Yang et al. Infect Drug Resist. .

Abstract

Purpose: RNA terminal phosphate cyclase like 1 (RCL1) undergoes overexpression during the immune response of Candida albicans following drug treatment. This study aims to investigate the expression levels of RCL1 in C. albicans under various stress conditions.

Methods: Fifteen itraconazole (ITR)-resistant strains of clinical C. albicans, and one standard strain were employed for RCL1 sequencing, and mutations in RCL1 were analyzed. Subsequently, 14 out of the 15 ITR-resistant clinical strains and 14 clinical strains sensitive to ITR, fluconazole (FCA) as well as voriconazole (VRC) were cultured under diverse conditions. The expression of RCL1 ITR-resistant and sensitive C. albicans was then assessed using real-time quantitative PCR (RT-qPCR) assays.

Results: Compared to the standard strain, three missense mutations (C6A, G10A, and A11T) were identified in the RCL1 gene of ITR-resistant C. albicans through successful forward sequencing. Additionally, using successful reverse sequencing, one synonymous mutation (C1T) and four missense mutations (C1T, A3T, A7G, and T8G) were found in the RCL1 gene of ITR-resistant C. albicans. RCL1 expression was significantly higher in ITR-resistant C. albicans than in sensitive strains under standard conditions (37°C, 0.03% CO2, pH 4.0). Low temperature (25°C) increased RCL1 expression in sensitive C. albicans while decreasing it in ITR-resistant strains. Elevated CO2 concentrations (5% CO2) had a negligible effect on RCL1 expression in sensitive C. albicans, but effectively reduced RCL1 level in ITR-resistant strains. Furthermore, a medium with a pH of 7 decreased the expression of RCL1 in both resistant and sensitive C. albicans.

Conclusion: This study demonstrated that RCL1 mutations in ITR-resistant C. albicans, and variations in culture conditions significantly influence RCL1 expression in both ITR-resistant and sensitive C. albicans, thereby inducing alterations in the dimorphism of C. albicans.

Keywords: Candida albicans; RCL1; culture conditions; itraconazole resistance.

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Conflict of interest statement

The authors declare that they have no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Expression of RCL1 in the sensitive and resistant C. albicans. (A) RCL1 expression in sensitive and ITR-resistant C. albicans in normal condition (37°C, 5% CO2, pH = 4.0). N = 14. (B) RCL1 expression in sensitive and ITR-resistant C. albicans at low temperature (25°C, 0.03% CO2, pH = 4.0). N = 14. (C) The level of RCL1 in sensitive and ITR-resistant C. albicans at high CO2 concentration (37°C, 5% CO2, pH = 4.0). N = 14. (D) The expression of RCL1 in sensitive and ITR-sensitive C. albicans in neutral conditions (37°C, 0.03% CO2, pH = 7.0). N = 14. *P < 005, compared with the sensitive strains.
Figure 2
Figure 2
Expression of RCL1 in C. albicans under diverse temperature conditions. (A) RCL1 expression in sensitive C. albicans at 37°C or 25°C. N = 14. (B) RCL1 expression in ITR-resistant C. albicans at 37°C or 25°C. N = 14. *P < 005, compared with the strains cultured at 37°C.
Figure 3
Figure 3
Expression of RCL1 in C. albicans under diverse CO2 condition. (A) The RCL1 level in sensitive C. albicans under 0.03% or 5% CO2 concentration. N = 14. (B) The RCL1 expression in ITR-resistant C. albicans under 0.03% or 5% CO2 concentration. N = 14. *P < 005, compared with the strains cultured with 0.03% CO2.
Figure 4
Figure 4
Expression of RCL1 in C. albicans under different pH condition. (A) The RCL1 expression in sensitive C. albicans under pH = 4 or pH = 7 condition. N = 14. (B) The RCL1 expression in ITR-resistant C. albicans under pH = 4 or pH = 7 condition. N = 14. *P < 005, compared with the strains cultured at pH = 4.
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