The Dynamics of Cryptococcus neoformans Cell and Transcriptional Remodeling during Infection

被引：7

作者：

Freitas, Gustavo J. C. ^{[1
]}

Gouveia-Eufrasio, Ludmila ^{[1
]}

Emidio, Eluzia C. P. ^{[1
]}

Carneiro, Hellem C. S. ^{[1
]}

Baltazar, Ludmila de Matos ^{[2
]}

Costa, Marliete C. ^{[1
]}

Frases, Susana ^{[3
]}

Araujo, Glauber R. de Sousa ^{[3
]}

Paixao, Tatiane A. ^{[4
]}

Sossai, Brunno G. ^{[4
]}

Caza, Melissa ^{[5
]}

Kronstad, James W. ^{[5
]}

Peres, Nalu T. A. ^{[1
]}

Santos, Daniel A. ^{[1
]}

机构：

[1] Univ Fed Minas Gerais, Dept Microbiol, Lab Micol, BR-31270901 Belo Horizonte, MG, Brazil

[2] Univ Fed Goias, Inst Patol Trop & Saude Publ, BR-74605020 Goiania, Go, Brazil

[3] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941902 Rio De Janeiro, Brazil

[4] Univ Fed Minas Gerais, Dept Patol, Lab Patol Celular & Mol, BR-31270901 Belo Horizonte, MG, Brazil

[5] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada

来源：

CELLS | 2022年 / 11卷 / 23期

基金：

加拿大健康研究院;

关键词：

cell size; ribosome biogenesis; inositol pathway; proteasome; cell remodeling; cryptococcosis; VIRULENCE; PULMONARY; ADAPTATION; MECHANISMS; MORPHOLOGY; RESPONSES; MELANIN; STRESS;

D O I：

10.3390/cells11233896

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 mu m) 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.

引用

页数：23

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