Exploring the roles of fungal extracellular vesicles in fungal pathogenesis and symbiosis: Current understandings and future perspectives.

Fungal extracellular vesicles (FEVs) have emerged as sophisticated emissaries in cross-kingdom communication, redefining our understanding of fungal secretome in pathogens like Cryptococcus neoformans and Candida species. Rather than mere cellular debris, these bilayered structures are actively exported across the fungal cell wall via complex biogenesis mechanisms, carrying a potent cargo of virulence factors, genetic material, proteins, lipids, and polysaccharides. In human hosts, FEVs facilitate myco-pathogenesis by interacting directly with immune cells to modulate the immune response, either triggering inflammation via recognition of their molecular signatures, or enabling immune evasion, thereby aiding fungal survival and dissemination. This biological activity presents dual clinical opportunities. FEVs can serve as specific biomarkers for the early diagnosis of invasive fungal infections, such as invasive aspergillosis, even in asymptomatic individuals, and they hold immense potential as novel vaccine candidates or engineered vehicles for targeted drug delivery. Beyond human pathology, this review highlights that these vesicles act as fundamental mediators of fungal symbiosis, driving processes like lichenization and arbuscular mycorrhization, which opens promising new avenues for research into sustainable agriculture and plant survival.