Extracellular Vesicle Formation in Cryptococcus deuterogattii Impacts Fungal Virulence and Requires the NOP16 Gene

• Published in: Infection and immunity Vol. 90; no. 8; p. e0023222
• Main Authors: Castelli, Rafael F, Pereira, Alana, Honorato, Leandro, Valdez, Alessandro, de Oliveira, Haroldo C, Bazioli, Jaqueline M, Garcia, Ane W A, Klimeck, Tabata D'Maiella Freitas, Reis, Flavia C G, Staats, Charley C, Nimrichter, Leonardo, Fill, Taícia P, Rodrigues, Marcio L
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 18.08.2022
• Subjects: Cell Communication; Cryptococcus - genetics; Eukaryotic Cells; Extracellular Vesicles - metabolism; Fungal and Parasitic Infections; Virulence - genetics; virulence; Cryptococcus; extracellular vesicles
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.00232-22

Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known. is a eukaryotic gene that is required for the activity of benzimidazoles against Cryptococcus deuterogattii. In this study, during the phenotypic characterization of mutants lacking expression, we observed that this gene was required for EV production. Analysis of the small molecule composition of EVs produced by wild-type cells and two independent Δ mutants revealed that the deletion of resulted not only in a reduced number of EVs but also an altered small molecule composition. In a Galleria mellonella model of infection, the Δ mutants were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were coinjected with the Δ cells in G. mellonella. These results reveal a role for in EV biogenesis and cargo, and also indicate that the composition of EVs is determinant for cryptococcal virulence.