The evaluation of the overexpression of the<i>ERG‐11</i>,<i>MDR‐1</i>,<i>CDR‐1</i>, and<i>CDR‐2</i>genes in fluconazole‐resistant<i>Candida albicans</i>isolated from Ahvazian cancer patients with oral candidiasis
Mehrnoush Maheronnaghsh, Ali Teimoori, Parvin Dehghan, Mahnaz Fatahinia
Abstract
INTRODUCTION: Resistance to azole drugs has been observed in candidiasis due to their long-term use and poor response to treatment. Resistance to azole drugs in Candida albicans isolates is controlled by several genes including ERG11, CDR1, CDR2, and MDR1. In this study, the expression of the mentioned genes was evaluated in C. albicans isolates susceptible and resistant to fluconazole. METHODS: After identifying the Candida isolates using morphological and molecular methods, the minimum inhibitory concentration (MIC) and drug susceptibility were determined using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. RNA was then extracted and cDNA was synthesized from 24 C. albicans isolates from patients with cancer. Then, the mean expressions of these genes were compared in two groups using real-time polymerase chain reaction (RT-PCR). RESULTS: A total of 74 Candida isolates were obtained from the oral cavity of 61 cancer patients with oral candidiasis. After 24 h, 21.6% of the isolates were fluconazole-resistant, 10.8% were identified as dose-dependent, and the rest of the isolates (67.6%) were fluconazole-sensitive. The mean expressions of the CDR1 and MDR1 genes were significantly higher in the resistant isolates than in the sensitive ones. However, the ERG11 and CDR2 genes were not significantly increased in the resistant isolates. CONCLUSION: The increased mean expressions of the CDR1 and MDR1 genes had a greater effect on fluconazole resistance among the drug-resistant strains of C. albicans in chemotherapy patients. It seemed that the accumulation of chemotherapeutic drugs in this organism stimulated some regulatory factors and increased the expression of these two genes and ultimately helped to further increase their expression and resistance to fluconazole.