Insights into the structure, function, and impact of Candida albicans UPC2 gene on azole resistance; a mini-review

TL;DR

This mini-review explores how the UPC2 gene in Candida albicans contributes to resistance against azole antifungal drugs.

Contribution

The paper provides a focused summary of the UPC2 gene's role in azole resistance mechanisms in C. albicans.

Findings

UPC2 enhances azole resistance by upregulating ergosterol biosynthesis genes like ERG2 and ERG11.

Increased ERG11 expression reduces azole susceptibility by boosting 14α-lanosterol demethylase production.

UPC2 also regulates sterol uptake and environmental adaptations, further supporting azole resistance.

Abstract

Candidiasis is a prevalent fungal infection caused by various species of Candida, especially, C. albicans.
The emergence of resistance to azole medications, which are frequently prescribed for the treatment of Candida infections, presents a significant challenge in
the management of these infections.

The present mini-review summarizes findings from a comprehensive search of articles published between 1999 and 2024, retrieved from Scopus, PubMed, and Web of Science.
Studies were selected using specific keywords based on relevance to UPC2 gene functions, azole resistance mechanisms, and C. albicans biology.

The UPC2 gene has become crucial in regulating drug resistance in C. albicans. This gene encodes a zinc (II)-Cys (6) transcription factor involved in
the biosynthesis of sterols and contributes to resistance against azole antifungal drugs. When exposed to azoles, UPC2 in C. albicans enhances the
expression of ergosterol biosynthesis genes, such as ERG2 and ERG11. Increased expression of ERG11 leads to reduced susceptibility
to azoles by boosting the production of 14α-lanosterol demethylase, the primary target of these antifungal agents. Furthermore, UPC2 regulates sterol uptake
under anaerobic conditions and manages other adaptations to environmental changes, all of which contribute to azole resistance.

Gaining insight into how the UPC2 gene contributes to azole resistance is essential for the development of effective strategies in the antifungal drug development process.

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