Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development

Ergosterol plays a dual role in fungal pathogenesis and azole resistance, driving key advancements in the understanding of its biosynthesis regulation. This review integrates the latest research progress on the regulation of fungal ergosterol biosynthesis and its role in drug resistance and pathogen...

Full description

Saved in:
Bibliographic Details
Main Authors: Lingyun Song, Sha Wang, Hang Zou, Xiaokang Yi, Shihan Jia, Rongpeng Li, Jinxing Song
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/13/4/862
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ergosterol plays a dual role in fungal pathogenesis and azole resistance, driving key advancements in the understanding of its biosynthesis regulation. This review integrates the latest research progress on the regulation of fungal ergosterol biosynthesis and its role in drug resistance and pathogenicity. We comprehensively discuss the functions of key enzymes (such as Erg11p/Cyp51A, Erg6p, Erg3p, and Erg25p) in the mevalonate, late, and alternative pathways. Notably, we highlight the complex regulation of <i>cyp51A</i> expression by factors such as SrbA, AtrR, CBC, HapX, and NCT in <i>Aspergillus fumigatus</i>, and elucidate the distinctive roles of Upc2, Adr1, and Rpn4 in <i>Candida</i> species. Importantly, we summarize recent discoveries on the CprA-dependent regulation of Cyp51A/Erg11p and heme-mediated stability control. Based on these findings, we propose innovative antifungal strategies, including dual-target inhibition and multi-enzyme inhibition by natural products, which provide novel insights and potential directions for the development of next-generation antifungal therapies.
ISSN:2076-2607