Fungicide resistance in Fusarium oxysporum: Advances in molecular, cellular, and metabolic mechanisms

Fusarium is a globally distributed genus of fungi, long recognized for its devastating impact on plants and, more recently, for its emergence as an etiological agent of human infections. Within this genus, the Fusarium oxysporum species complex (FOSC) stands out as a group of critical dual-threat pathogens: certain members induce vascular wilt in over 100 crop species, while others cause fusariosis in humans. Currently, the sustainable management of vascular wilt and the effective treatment of fusariosis are compromised by the increasing resistance of F. oxysporum to major fungicide classes, largely driven by excessive agricultural fungicide use. To date, fungicide resistance mechanisms in F. oxysporum can be broadly classified into target-site and non-target-site mechanisms. Target-site mutations remain the most frequently reported, but in some cases, resistance involves more complex or potentially species-specific mechanisms. Non-target-site resistance includes transcriptional reprogramming in response to fungicide exposure, leading to overexpression of genes involved in the cell envelope and transporters that export fungicides, as well as the production of secondary metabolites under fungicide stress. However, the roles of mutations in other coding and regulatory regions, the importance of the genomic adaptive responses to fungicides remain largely unexplored. This review aims to provide a deeper understanding of the dynamic interplay between fungicides and the FOSC by synthesizing current advances in the mechanisms of fungicide resistance, with a particular focus on F. oxysporum strains and their adaptative mechanisms that enable these fungi to resist fungicides.