Molecular Evaluation of the mRNA Expression of the , , , and Genes Linked to Fluconazole Resistance in in a Colombian Population.

INTRODUCTION

The study of 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 by analyzing the , , , and 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 to fluconazole.

RESULTS

The relative expression of the , , and 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 , 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 that was lower than the median number of contacts between fluconazole and , -, and -. 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 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.