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. 2024 Jul 22;10(7):509.
doi: 10.3390/jof10070509.

Molecular Evaluation of the mRNA Expression of the ERG11, ERG3, CgCDR1, and CgSNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population

Leidy Yurany Cárdenas Parra  1   2 , Ana Elisa Rojas Rodríguez  2 , Jorge Enrique Pérez Cárdenas  1 , Juan Manuel Pérez-Agudelo  1
Affiliations

Molecular Evaluation of the mRNA Expression of the ERG11, ERG3, CgCDR1, and CgSNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population

Leidy Yurany Cárdenas Parra et al. J Fungi (Basel). .

Abstract

Introduction: The study of Candida glabrata genes associated with fluconazole resistance, from a molecular perspective, increases the understanding of the phenomenon with a view to its clinical applicability.

Objective: We sought to establish the predictive molecular profile of fluconazole resistance in Candida glabrata by analyzing the ERG11, ERG3, CgCDR1, and CgSNQ2 genes.

Method: Expression was quantified using RT-qPCR. Metrics were obtained through molecular docking and Fisher discriminant functions. Additionally, a predictive classification was made against the susceptibility of C. glabrata to fluconazole.

Results: The relative expression of the ERG3, CgCDR1, and CgSNQ2 genes was higher in the fluconazole-resistant strains than in the fluconazole-susceptible, dose-dependent strains. The gene with the highest relative expression in the fluconazole-exposed strains was CgCDR1, and in both the resistant and susceptible, dose-dependent strains exposed to fluconazole, this was also the case. The molecular docking model generated a median number of contacts between fluconazole and ERG11 that was lower than the median number of contacts between fluconazole and ERG3, -CgCDR1, and -CgSNQ2. The predicted classification through the multivariate model for fluconazole susceptibility achieved an accuracy of 73.5%.

Conclusion: The resistant strains had significant expression levels of genes encoding efflux pumps and the ERG3 gene. Molecular analysis makes the identification of a low affinity between fluconazole and its pharmacological target possible, which may explain the lower intrinsic susceptibility of the fungus to fluconazole.

Keywords: Candida glabrata; fluconazole; fungal drug resistance; molecular docking simulation; multivariate analysis; reverse transcriptase polymerase chain reaction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Relative expression levels of the CgCDR1 gene for strains not exposed vs. strains exposed to fluconazole. (B) Relative expression levels of the ERG11 gene for strains not exposed vs. strains exposed to fluconazole. (C) Relative expression levels of the ERG3 gene for strains not exposed vs. strains exposed to fluconazole. (D) Relative expression levels of the CgSNQ2 gene for strains not exposed vs. strains exposed to fluconazole.
Figure 2
Figure 2
Relative expression of the CgCDR1 gene according to susceptibility profile and the exposure to fluconazole.
Figure 3
Figure 3
Relative expression of the ERG11 gene according to susceptibility profile and the exposure to fluconazole.
Figure 4
Figure 4
Relative expression of the ERG3 gene according to susceptibility profile and the exposure to fluconazole.
Figure 5
Figure 5
Relative expression of the CgSNQ2 gene according to susceptibility profile and the exposure to fluconazole.
Figure 6
Figure 6
Comparative representations of fluconazole and the proteins of interest docking. (A) Three-dimensional presentation of the molecular relationship (docking) between fluconazole and ERG11. (B) Three-dimensional presentation of the molecular relationship between fluconazole and CgCDR1. Hydrophobic interactions with the residues are shown with dashed gray lines and with gray surfaces on the proteins.
See this image and copyright information in PMC

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