Fungal Extracellular Vesicles Are Involved in Intraspecies Intracellular Communication

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Bitencourt, Tamires A. ; Hatanaka, Otavio ; Pessoni, Andre M. ; Freitas, Mateus S. ; Trentin, Gabriel ; Santos, Patrick ; Rossi, Antonio ; Martinez-Rossi, Nilce M. ; Alves, Lysangela L. ; Casadevall, Arturo ; Rodrigues, Marcio L. ; Almeida, Fausto

• Document type: Journal article
• Source: MBIO; v. 13, n. 1, p. 14-pg., 2022-01-01.

Abstract

Fungal infections are associated with high mortality rates in humans. The risk of fungal diseases creates the urgent need to broaden the knowledge base regard-ing their pathophysiology. In this sense, the role of extracellular vesicles (EVs) has been described to convey biological information and participate in the fungus-host interaction process. We hypothesized that fungal EVs work as an additional element in the communication routes regulating fungal responses in intraspecies interaction systems. In this respect, the aim of this study was to address the gene regulation profiles prompted by fungal EVs in intraspecies recipient cells. Our data demonstrated the intraspecies uptake of EVs in pathogenic fungi, such as Candida albicans, Aspergillus fumigatus, and Paracoccidioides brasiliensis, and the effects triggered by EVs in fungal cells. In C. albicans, we evaluated the involvement of EVs in the yeast-to-hypha transition, while in P. brasiliensis and A. fumigatus the function of EVs as stress transducers was investigated. P. brasiliensis and A. fumigatus were exposed to an inhibitor of glycosylation or UV light, respectively. The results demonstrated the role of EVs in regulating the expression of target genes and triggering phenotypic changes. The EVs treatment induced cellular proliferation and boosted the yeast to hyphal transition in C. albicans, while they enhanced stress responsiveness in A. fumigatus and P. brasiliensis, establishing a role for EVs in fungal intraspecies communication. Thus, EVs regulate fungal behavior, acting as potent message effectors, and under-standing their effects and mechanism(s) of action could be exploited in antifungal therapies. IMPORTANCE Here, we report a study about extracellular vesicles (EVs) as communication mediators in fungi. Our results demonstrated the role of EVs from Candida albicans, Aspergillus fumigatus, and Paracoccidioides brasiliensis regulating the expression of target genes and phenotypic features. We asked whether fungal EVs play a role as message effectors. We show that fungal EVs are involved in fungal interaction systems as potent message effectors, and understanding their effects and mechanisms of action could be exploited in antifungal therapies. (AU)

• FAPESP's process: 19/02504-2 - Production and composition evaluation of extracellular vesicles from Aspergillus fumigatus
• Grantee: André Moreira Pessoni
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/22596-9 - Molecular mechanisms associated with pathogenicity and resistance in fungi: strategies for treating dermatophytosis
• Grantee: Nilce Maria Martinez-Rossi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/03322-7 - Role of galectin-3 in the Cryptococcus neoformans infection
• Grantee: Fausto Bruno dos Reis Almeida
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/22454-0 - Evaluation of the immunomodulatory potential of extracellular vesicles produced by Aspergillus fumigatus
• Grantee: Mateus Silveira Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate