Extracellular vesicle formation in<i>Cryptococcus deuterogattii</i>impacts fungal virulence and requires the<i>NOP16</i>gene
Abstract Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known.NOP16is a eukaryotic gene that is required for the activity of benzimidazoles againstCryptococcus deuterogattii. In this study, during the phenotypic characterization ofC. deuterogattiimutants lackingNOP16expression, 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 independentnop16Δ mutants revealed that the deletion ofNOP16resulted not only in a reduced number of EVs but also an altered small molecule composition. In aGalleria mellonellamodel of infection, thenop16Δ mutants were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were co-injected with thenop16Δ cells inG. mellonella. These results reveal a role forNOP16in EV biogenesis and cargo, and also indicate that the composition of EVs is determinant for cryptococcal virulence..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 22. Nov. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Castelli, Rafael F. [VerfasserIn] |
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doi: |
10.1101/2022.06.06.494995 |
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funding: |
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PPN (Katalog-ID): |
XBI036211869 |
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520 | |a Abstract Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known.NOP16is a eukaryotic gene that is required for the activity of benzimidazoles againstCryptococcus deuterogattii. In this study, during the phenotypic characterization ofC. deuterogattiimutants lackingNOP16expression, 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 independentnop16Δ mutants revealed that the deletion ofNOP16resulted not only in a reduced number of EVs but also an altered small molecule composition. In aGalleria mellonellamodel of infection, thenop16Δ mutants were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were co-injected with thenop16Δ cells inG. mellonella. These results reveal a role forNOP16in EV biogenesis and cargo, and also indicate that the composition of EVs is determinant for cryptococcal virulence. | ||
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700 | 1 | |a Honorato, Leandro |4 aut | |
700 | 1 | |a Valdez, Alessandro |4 aut | |
700 | 1 | |a de Oliveira, Haroldo C. |4 aut | |
700 | 1 | |a Bazioli, Jaqueline M. |4 aut | |
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700 | 1 | |a Freitas Klimeck, Tabata D’Maiella |4 aut | |
700 | 1 | |a Reis, Flavia C. G. |4 aut | |
700 | 1 | |a Staats, Charley C. |4 aut | |
700 | 1 | |a Nimrichter, Leonardo |4 aut | |
700 | 1 | |a Fill, Taícia P. |4 aut | |
700 | 1 | |a Rodrigues, Marcio L. |0 (orcid)0000-0002-6081-3439 |4 aut | |
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