Proteomics

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Extracellular vesicle formation in Cryptococcus deuterogattii impacts fungal virulence


ABSTRACT: Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known. NOP16 is a eukaryotic gene that is required for the activity of benzimidazoles against Cryptococcus deuterogattii. In this study, during the phenotypic characterization of C. deuterogattii mutants expected to lack NOP16 expression, we observed a reduced EV production. Whole-genome sequencing, RNAseq, and cellular proteomics revealed that, contrary to our initial findings, these mutants expressed Nop16 but exhibited altered expression of 14 genes potentially involved in sugar transport. Based on this observation, we designated these mutants as past1 and past2, representing potentially altered sugar transport. Analysis of the small molecule composition of EVs produced by wild-type cells and the past1 and past2 mutants revealed not only a reduced number of EVs but also an altered small molecule composition. In a Galleria mellonella model of infection, the past1 and past2 mutants were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were co-injected with the mutant cells in G. mellonella. These results connect EV biogenesis, cargo and cryptococcal virulence.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Cryptococcus Gattii Vgii R265

SUBMITTER: Marlon D M Santos  

LAB HEAD: Marcio L. Rodrigues

PROVIDER: PXD048601 | Pride | 2024-02-29

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20221118_117922_RAFAEL_1_2.raw Raw
20221118_117922_RAFAEL_1_2.yada.ctxt Other
20221118_117922_RAFAEL_1_3.raw Raw
20221118_118022_RAFAEL_2_1.raw Raw
20221118_118022_RAFAEL_2_2.raw Raw
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