The evaluation of the overexpression of theERG‐11,MDR‐1,CDR‐1, andCDR‐2genes in fluconazole‐resistantCandida albicansisolated from Ahvazian cancer patients with oral candidiasis

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.

Effect of new methionine-based ionic liquid on the CDR1 and CDR2 gene expression on sensitive and resistant strains of Candida albicans

“…Candida albicans is the most causative agent of candidiasis, especially in critical and immunocompromised patients. One of the challenges in developing new antifungal drugs is the overexpression of the CDR1 and CDR2 efflux pumps that cause resistance against the common antifungal medications ( 17 ). Emerging ILs with unique properties of the elongated against the fungal agents, lead the researchers to apply them as new safe administrations against fungi ( 17 ).…”

“…One of the challenges in developing new antifungal drugs is the overexpression of the CDR1 and CDR2 efflux pumps that cause resistance against the common antifungal medications ( 17 ). Emerging ILs with unique properties of the elongated against the fungal agents, lead the researchers to apply them as new safe administrations against fungi ( 17 ). Some of the investigators demonstrated the antimicrobial function of various ionic liquids ( 12 , 32 ).…”

“…The process was denaturation at 95°C for 30 sec, annealing at 57°C for 30 sec, extension at 72°C for 30 sec, and the last step of reaction at 72°C for 5 min. The base design of the primers used for this step to investigate the presence of the gene from clinical samples of C. albicans originated from research and synthesized by SINA COLON.CO, Iran ( 17 ).…”

“…The mutants harboring a deletion of CDR1, CDR2, or MDR1 increase susceptibility to fluconazole in planktonic form. Candida biofilm development and resistance could be with various mechanisms that may involve different molecular factors ( 17 ).…”

Metal Nanoparticles to Combat Candida albicans Infections: An Update

“…Interestingly, these authors also verified that AgNPs treatment reduced the membrane content of Cdr1p and Cdr2p, and thus efflux pump activity. FCZ-resistant C. albicans strains usually exhibit overexpression or increased efflux pump activity, which reduces their susceptibility to antifungal agents [ 48 , 49 ]. In this case, exposure to AgNPs restored the FCZ susceptibility phenotype of the resistant strains.…”