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Transcriptional and Post-Translational Roles of Calcineurin in Cationic Stress and Glycerol Biosynthesis in Cryptococcus neoformans.
Santos, Ronaldo Silva; Martins-Silva, Gabriel; Padilla, Adrián Adolfo Álvarez; Possari, Mateus; Degello, Sérgio Donnantuoni; Bernardes Brustolini, Otávio J; Vasconcelos, Ana Tereza Ribeiro; Vallim, Marcelo Afonso; Pascon, Renata C.
Afiliação
  • Santos RS; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
  • Martins-Silva G; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
  • Padilla AAÁ; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
  • Possari M; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
  • Degello SD; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
  • Bernardes Brustolini OJ; Laboratório Nacional de Computação Científica-LNCC, Labinfo-Laboratório de Bioinformática, Petrópolis 25651-075, RJ, Brazil.
  • Vasconcelos ATR; Laboratório Nacional de Computação Científica-LNCC, Labinfo-Laboratório de Bioinformática, Petrópolis 25651-075, RJ, Brazil.
  • Vallim MA; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
  • Pascon RC; Universidade Federal de São Paulo, Campus Diadema, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
J Fungi (Basel) ; 10(8)2024 Jul 30.
Article em En | MEDLINE | ID: mdl-39194857
ABSTRACT
Stress management is an adaptive advantage for survival in adverse environments. Pathogens face this challenge during host colonization, requiring an appropriate stress response to establish infection. The fungal pathogen Cryptococcus neoformans undergoes thermal, oxidative, and osmotic stresses in the environment and animal host. Signaling systems controlled by Ras1, Hog1, and calcineurin respond to high temperatures and osmotic stress. Cationic stress caused by Na+, K+, and Li+ can be overcome with glycerol, the preferred osmolyte. Deleting the glycerol phosphate phosphatase gene (GPP2) prevents cells from accumulating glycerol due to a block in the last step of its biosynthetic pathway. Gpp2 accumulates in a phosphorylated form in a cna1Δ strain, and a physical interaction between Gpp2 and Cna1 was found; moreover, the gpp2Δ strain undergoes slow growth and has attenuated virulence in animal models of infection. We provide biochemical evidence that growth in 1 M NaCl increases glycerol content in the wild type, whereas gpp2Δ, cna1Δ, and cnb1Δ mutants fail to accumulate it. The deletion of cnb1Δ or cna1Δ renders yeast cells sensitive to cationic stress, and the Gfp-Gpp2 protein assumes an abnormal localization. We suggest a mechanism in which calcineurin controls Gpp2 at the post-translational level, affecting its localization and activity, leading to glycerol biosynthesis. Also, we showed the transcriptional profile of glycerol-deficient mutants and established the cationic stress response mediated by calcineurin; among the biological processes differentially expressed are carbon utilization, translation, transmembrane transport, glutathione metabolism, oxidative stress response, and transcription regulation. To our knowledge, this is the first time that this transcriptional profile has been described. These results have implications for pathogen stress adaptability.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Fungi (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Fungi (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça