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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\u00a0neoformans, cell size reduction (cell body \u2264 3 \u00b5m) 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/cells11233896","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T03:55:37Z","timestamp":1669953337000},"page":"3896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Dynamics of Cryptococcus neoformans Cell and Transcriptional Remodeling during Infection"],"prefix":"10.3390","volume":"11","author":[{"given":"Gustavo J. C.","family":"Freitas","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Gouveia-Eufrasio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eluzia C. P.","family":"Emidio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hellem C. S.","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"de Matos Baltazar","sequence":"additional","affiliation":[{"name":"Instituto de Patologia Tropical e Sa\u00fade P\u00fablica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marliete C.","family":"Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Frases","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura Celular Hertha Meyer, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5478-9006","authenticated-orcid":false,"given":"Glauber R.","family":"de Sousa Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura Celular Hertha Meyer, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane A.","family":"Paix\u00e3o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Celular e Molecular, Departamento de Patologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunno G.","family":"Sossai","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Celular e Molecular, Departamento de Patologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Caza","sequence":"additional","affiliation":[{"name":"Michael Smith Labs, University of British Columbia, Vancouver, V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-6976","authenticated-orcid":false,"given":"James W.","family":"Kronstad","sequence":"additional","affiliation":[{"name":"Michael Smith Labs, University of British Columbia, Vancouver, V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2762-3200","authenticated-orcid":false,"given":"Nalu T. A.","family":"Peres","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-5666","authenticated-orcid":false,"given":"Daniel A.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1128\/CMR.00126-13","article-title":"Cryptococcus gattii infections","volume":"27","author":"Chen","year":"2014","journal-title":"Clin. Microbiol. 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