Azole Resistance in Candida albicans Isolates from Oropharyngeal Candidiasis is Associated with ERG11 Mutation and Efflux Overexpression

Abstract

Background: Azole resistance rates are rising in Candida species. Fluconazole is one of the most important antifungal drugs used in candidiasis treatment. Objectives: We identified the molecular mechanisms of fluconazole resistance of Candida albicans oropharyngeal candidiasis (OPC) isolates obtained from head and neck cancer patients, a study carried out between 2018 and 2020. Methods: One hundred and twenty-five C. albicans clinical isolates were collected. Antifungal susceptibilities were determined by the CLSI- M27-A3 method. The ERG11 gene was amplified and sequenced to discover SNP mutation. Moreover, real-time PCR was carried out to measure the mRNA levels of ERG11, CDR1, CDR2, and MDR1. Results: Resistance to fluconazole was found in 15 C. albicans isolates. Amino acid substitutions E266D and D116E were observed in resistant, sensitive dose-dependent (SDD), and susceptible C. albicans isolates. K128T, G465S, A114S, Y257H and V488I were in relation to fluconazole resistance. D504A, P375A, W520C, G59S, and V51L were novel substitutions detected in the isolates; except for D504A, other mutations were observed only in resistance isolates. The expression levels of CDR2, CDR1, MDR1, and ERG11 were increased compared to susceptible isolates, respectively. Conclusions: ERG11 mutation was the principal mechanism for fluconazole resistance in C. albicans isolated from oropharyngeal candidiasis patients, and caspofungin can be used as the effective antifungal substance in fluconazole resistance situation for C. albicans infection.