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The Dynamics of Cryptococcus neoformans Cell and Transcriptional Remodeling during Infection Freitas, Gustavo J. C.; Gouveia-Eufrasio, Ludmila; Emidio, Eluzia C. P.; Carneiro, Hellem C. S.; de Matos Baltazar, Ludmila; Costa, Marliete C.; Frases, Susana; de Sousa Araújo, Glauber R.; Paixão, Tatiane A.; Sossai, Brunno G.; Caza, Melissa; Kronstad, James Warren; Peres, Nalu T. A.; Santos, Daniel A.

Abstract

The phenotypic plasticity of Cryptococcus neoformans is widely studied and demonstrated in vitro, but its influence on pathogenicity remains unclear. In this study, we investigated the dynamics of cryptococcal cell and transcriptional remodeling during pulmonary infection in a murine model. We showed that in Cryptococcus neoformans, cell size reduction (cell body ≤ 3 µm) is important for initial adaptation during infection. This change was associated with reproductive fitness and tissue invasion. Subsequently, the fungus develops mechanisms aimed at resistance to the host’s immune response, which is determinant for virulence. We investigated the transcriptional changes involved in this cellular remodeling and found an upregulation of transcripts related to ribosome biogenesis at the beginning (6 h) of infection and a later (10 days) upregulation of transcripts involved in the inositol pathway, energy production, and the proteasome. Consistent with a role for the proteasome, we found that its inhibition delayed cell remodeling during infection with the H99 strain. Altogether, these results further our understanding of the infection biology of C. neoformans and provide perspectives to support therapeutic and diagnostic targets for cryptococcosis.

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Title
The Dynamics of Cryptococcus neoformans Cell and Transcriptional Remodeling during Infection
Creator
Freitas, Gustavo J. C.; Gouveia-Eufrasio, Ludmila; Emidio, Eluzia C. P.; Carneiro, Hellem C. S.; de Matos Baltazar, Ludmila; Costa, Marliete C.; Frases, Susana; de Sousa Araújo, Glauber R.; Paixão, Tatiane A.; Sossai, Brunno G.; Caza, Melissa; Kronstad, James Warren; Peres, Nalu T. A.; Santos, Daniel A.
Contributor
Michael Smith Laboratories
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2022-12-02
Description
The phenotypic plasticity of Cryptococcus neoformans is widely studied and demonstrated in vitro, but its influence on pathogenicity remains unclear. In this study, we investigated the dynamics of cryptococcal cell and transcriptional remodeling during pulmonary infection in a murine model. We showed that in Cryptococcus neoformans, cell size reduction (cell body ≤ 3 µm) is important for initial adaptation during infection. This change was associated with reproductive fitness and tissue invasion. Subsequently, the fungus develops mechanisms aimed at resistance to the host’s immune response, which is determinant for virulence. We investigated the transcriptional changes involved in this cellular remodeling and found an upregulation of transcripts related to ribosome biogenesis at the beginning (6 h) of infection and a later (10 days) upregulation of transcripts involved in the inositol pathway, energy production, and the proteasome. Consistent with a role for the proteasome, we found that its inhibition delayed cell remodeling during infection with the H99 strain. Altogether, these results further our understanding of the infection biology of C. neoformans and provide perspectives to support therapeutic and diagnostic targets for cryptococcosis.
Subject
cell size; ribosome biogenesis; inositol pathway; proteasome; cell remodeling; cryptococcosis
Genre
Article
Type
Text
Language
eng
Date Available
2023-11-20
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0437784
URI
http://hdl.handle.net/2429/86630
Affiliation
Other UBC; Non UBC
Citation
Cells 11 (23): 3896 (2022)
Publisher DOI
10.3390/cells11233896
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0