Is there a difference in the expression levels of genes responsible for fluconazole resistance in Candida albicans isolated from people with different underlying diseases? A systematic review

Abstract

BACKGROUND AND PURPOSE: Fluconazole is one of the primary antifungal agents in the treatment of candidiasis. However, long-term treatment and indiscriminate use of drugs from the azole family have created resistant isolates. Candida albicans cells can develop resistance to fluconazole through various mechanisms. The present study aimed to investigate the expression of genes involved in fluconazole resistance in C. albicans in people with different underlying diseases. MATERIALS AND METHODS: Databases, such as PubMed, Scopus, and Web of Science were used to collect studies evaluating the expression levels of key C. albicans genes associated with fluconazole resistance from 1997 to 2024. Finally, 25 out of the 1,096 extracted studies were selected based on the inclusion and exclusion criteria. RESULTS: This systematic review identified the genes encoding the ATP-binding cassette membrane pump (CDR1, CDR2) and the genes encoding the major facilitator superfamily pumps (MDR1), as well as the ERG11 gene, are the most important effective genes in creating resistance of C. albicans to fluconazole. Based on the studies conducted since 1995, the CDR1 gene has the highest gene expression among the genes involved in resistance, followed by ERG11, MDR1, and CDR2, respectively. CONCLUSION: Comprehensive information about the activity of the genes and more studies on the genes involved in resistance, could provide valuable insights for further studies, prevent the occurrence of resistance to fluconazole and other azoles, and provide suitable treatments. The disease, as well as the dosage and duration of the antifungal therapy, may play an important role in determining the type of resistance mechanism of C. albicans. Therefore, further evaluation of the role of these genes in fluconazole-resistant species, along with their related gene products, is necessary.