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bioRxiv · 10.1101/2021.06.03.447024

Fungal extracellular vesicles are involved in intraspecies intracellular communication

Bittencourt, T. A.·Hatanaka, O.·Pessoni, A. M.·Freitas, M. S.·Trentin, G.·Santos, P.·Rossi, A.·Martinez-Rossi, N. M.·Alves, L. R.·Casadevall, A.·Rodrigues, M.·Almeida, F.
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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 regarding their pathophysiology. In this sense, the role of extracellular vesicles (EVs) has been described to convey biological information and participate in the fungal-host interaction process. EVs play many roles, including cellular physiology, responding to environmental cues, mediating a complex circuit of cellular communication in bidirectional crosstalk with other organisms, and the communication between fungal cells has been speculated. This study demonstrated the intra species uptake of EVs in fungi, including 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 yeast to hyphae transition, whilst in P. brasiliensis and A. fumigatus the function of EVs as stress transducers was investigated. Both 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 phenotype features. The EVs treatment induced cellular proliferation and boosted the transition yeast to hyphal transition in C. albicans, while they enhanced stress signals in A. fumigatus and P. brasiliensis, establishing a role for EVs in fungal intra species communication. Thus, fungal EVs regulate the virulence and adaptive traits in fungal interaction systems as potent message effectors, and understanding their effects and mechanism(s) of action could be exploited in antifungal therapies. Author SummaryExtracellular vesicles (EVs) play an important role in export systems. They act as vehicles for the transference of complex cargoes with broad biological functions, such as proteins, carbohydrates, pigments, nucleic acids, and lipids. EVs can contribute to fungal infection outcomes. The EV content exerts immunomodulatory functions during fungus-host interactions. Furthermore, the participation of EVs in communication between fungal cells has been speculated. This study investigated the capacity of EVs to mediate intra-species in three genera of human pathogenic fungi and established a regulatory function of EVs. We also assessed the features of this regulation by analyzing the cellular morphological aspects of fungi after stimulation with EVs. Our data suggest fungal EVs can function as potent signal mediators that mediate virulence and adaptive responses.

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Bittencourt, T. A., Hatanaka, O., Pessoni, A. M., Freitas, M. S., Trentin, G., Santos, P., Rossi, A., Martinez-Rossi, N. M., Alves, L. R., Casadevall, A., Rodrigues, M., Almeida, F.. 2021-06-05. Fungal extracellular vesicles are involved in intraspecies intracellular communication. https://doi.org/10.1101/2021.06.03.447024

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