Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Molecular and Associative Evaluation of ERG11, ERG3, CDR1, and SNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population

Version 1 : Received: 11 October 2023 / Approved: 11 October 2023 / Online: 11 October 2023 (12:24:15 CEST)

How to cite: Cárdenas Parra, L. Y.; Rojas Rodríguez, A. E.; Pérez Cárdenas, J. E.; Pérez-Agudelo, J. M. Molecular and Associative Evaluation of ERG11, ERG3, CDR1, and SNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population. Preprints 2023, 2023100708. https://doi.org/10.20944/preprints202310.0708.v1 Cárdenas Parra, L. Y.; Rojas Rodríguez, A. E.; Pérez Cárdenas, J. E.; Pérez-Agudelo, J. M. Molecular and Associative Evaluation of ERG11, ERG3, CDR1, and SNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population. Preprints 2023, 2023100708. https://doi.org/10.20944/preprints202310.0708.v1

Abstract

The resistance of Candida spp to fluconazole is a serious problem; Therefore, it must be investigated to expand the understanding of the phenomenon with a view to its clinical applicability. The aim was to evaluate the expression of ERG3, ERG11, CDR1, and SNQ2 genes involving computational analysis. Relative expression was quantified by RT-qPCR. Metrics were obtained by molecular docking and through Fisher's discriminant functions, a predictive classification against susceptibility to fluconazole was performed. The expression of ERG3, CDR1, and SNQ2 genes was higher in resistant strains than in dose-dependent sensitive strains. The gene with the highest expression in strains exposed to fluconazole was CDR1 and, in both resistant and dose-dependent sensitive strains exposed to fluconazole, the ERG11 gene had lower expression. The molecular docking model generated lower median fluconazole-ERG11 contacts than the median fluconazole-ERG3, -CDR1, and -SNQ2 contacts. The predicted classification through the multivariate model for fluconazole sensitivity obtained an accuracy of 73.5%. Resistant strains had a significant expression of CDR1, SNQ2 and ERG3 genes, compared to a comparatively low expression of ERG11. Molecular analysis identified a low affinity between fluconazole and its drug target, which may explain a lower intrinsic susceptibility of the fungus.

Keywords

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

Subject

Public Health and Healthcare, Other

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