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Azole Resistance in Candida Albicans Isolates From Oropharyngeal Candidiasis Is Associated With Erg11 Mutation and Efflux Overexpression Publisher



Jahanshiri Z1 ; Manifar S2 ; Arastehnazar F3 ; Hatami F4 ; Lotfali E5
Authors
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Authors Affiliations
  1. 1. Department of Mycology, Pasteur Institute of Iran, Tehran, Iran
  2. 2. Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, Cancer Institute of Tehran, Imam Khomeini Hospital Complex, Tehran, Iran
  3. 3. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
  4. 4. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  5. 5. Deptartment of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Jundishapur Journal of Microbiology Published:2022


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 Candida albicans clinical isolates were collected. Antifungal susceptibilities were deter-mined 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. © 2022, Author(s).
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