The dynamics of Cyptococcus neoformans cell and transcriptional remodeling during infection

• Autor(a) principal: Gustavo J. C. Freitas
• Data de Publicação: 2022
• Outros Autores: Brunno G. Sossai, Melissa Caza, James W. Kronstad, Nalu T. A. Peres, Daniel de Assis Santos, Ludmila Gouveia-eufrasio, Eluzia C. P. Emidio, Hellem C. S. Carneiro, Ludmila de Matos Baltazar, Marliete C. Costa, Susana Frases, Glauber R. de Sousa Araújo, Tatiane A. Paixão
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://www.mdpi.com/2073-4409/11/23/3896; http://hdl.handle.net/1843/60278; https://orcid.org/0000-0003-2762-3200; https://orcid.org/0000-0002-1108-5666; https://orcid.org/0000-0002-5478-9006
• topic: Cell size; Ribosome biogenesis; Inositol pathway; Proteasome; Cell remodeling; Cryptococcosis; Tamanho celular; Biogênese de organelas; Inositol; Criptococose; Biologia celular

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.