Extracellular vesicles produced by Malassezia commensal yeasts

Malassezia species were long regarded as microorganisms implicated exclusively in dermatological pathology. However, recent studies have further postulated a potential association between these fungi and systemic and non-cutaneous diseases, including inflammatory bowel disease, Crohn's disease, pancreatic cancer or neurodegenerative diseases, though evidence is still preliminary. Concurrently, there is growing scientific interest in extracellular vesicles as conserved cross-kingdom mediators of intercellular communication, with the capacity to modulate host cellular responses. While extracellular vesicles have been well characterized for various microorganisms, those secreted by Malassezia, specified as MalaEx, remain largely underexplored to this date. This review summarizes the current knowledge of MalaEx composition and their functional significance. Detailed analyses of MalaEx have revealed that their cargo includes various enzymes, importantly aspartyl proteases, as well as allergens, with a significant enrichment of Mala s1 and Mala s7 proteins. Additionally, small RNAs were identified among the transported molecules, however, bioinformatic analyses indicated that these RNAs cannot be classified as microRNAs (miRNAs). Importantly, MalaEx have been demonstrated to interact with human immune and cutaneous cells, thereby modulating inflammatory responses. These fungal structures may also play a protective role by limiting growth of pathogenic bacteria such as Staphylococcus aureus, overall suggesting broader relevance of MalaEx's functional role in regulating cutaneous microbial homeostasis and modulating the balance between pathogenic, commensal, and beneficial interactions in the skin ecosystem.