| Texto completo | |
| Autor(es): |
da Silva, Jeyson Pereira
;
Meneghini, Mariana Reis
;
Santos, Ronaldo Silva
;
Alves, Veronica Lira
;
Martho, Kevin Felipe da Cruz
;
Vallim, Marcelo Afonso
;
Pascon, Renata Castiglioni
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | SCIENTIFIC REPORTS; v. 13, n. 1, p. 16-pg., 2023-07-20. |
| Resumo | |
Fungal pathogens are a major cause of death, especially among immunocompromised patients. Therapies against invasive fungal infections are restricted to a few antifungals; therefore, novel therapies are necessary. Nutritional signaling and regulation are important for pathogen establishment in the host. In Cryptococcus neoformans, the causal agent of fungal meningitis, amino acid uptake and biosynthesis are major aspects of nutritional adaptation. Disruptions in these pathways lead to virulence attenuation in an animal model of infection, especially for sulfur uptake and sulfur amino acid biosynthesis. Deletion of Cys3, the main transcription factor that controls these pathways, is the most deleterious gene knockout in vitro and in vivo, making it an important target for further application. Previously, we demonstrated that Cys3 is part of a protein complex, including calcineurin, which is necessary to maintain high Cys3 protein levels during sulfur uptake and sulfur amino acid biosynthesis. In the current study, other aspects of Cys3 regulation are explored. Two lines of evidence suggest that C. neoformans Cys3 does not interact with the F-box WD40 protein annotated as Met30, indicating another protein mediates Cys3 ubiquitin degradation. However, we found another level of Cys3 regulation, which involves protein interactions between Cys3 and ATP sulfurylase (MET3 gene). We show that an atypical leucine zipper at the N-terminus of ATP sulfurylase is essential for physical interaction with Cys3 and calcineurin. Our data suggests that Cys3 and ATP sulfurylase interact to regulate Cys3 transcriptional activity. This work evidences the complexity involved in the regulation of a transcription factor essential for the sulfur metabolism, which is a biological process important to nutritional adaptation, oxidative stress response, nucleic acid stability, and methylation. This information may be useful in designing novel therapies against fungal infections. (AU) | |
| Processo FAPESP: | 18/20390-1 - Estudo dos elementos regulatórios que controlam a captação de aminoácidos em Cryptococcus neoformans |
| Beneficiário: | Kevin Felipe Cruz Martho |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 20/01000-8 - Cryptococcus neoformans e as relações entre virulência, metabolismo do enxofre, estresse osmótico e oxidativo |
| Beneficiário: | Renata Castiglioni Pascon |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/06290-7 - O complexo calcineurina e a resposta ao estresse osmótico e oxidativo: o papel da fosfatase Gpp2 e da via de biossíntese dos aminoácidos sulfurosos |
| Beneficiário: | Ronaldo Silva Santos |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 19/12051-5 - ATP sulfurilase: sua relação com o fator de transcrição Cys3 e a regulação da biossíntese dos aminoácidos sulfurosos em Cryptococcus neoformans |
| Beneficiário: | Mariana Reis Meneghini |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 21/00725-1 - Dissecando a estrutura da proteína ATP sulforilase codificada pelo gene MET3 e a relação com o fator de transcrição Cys3 para a virulência de C. neoformans |
| Beneficiário: | Jeyson Pereira da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 15/04400-9 - O papel da autofagia no crescimento a alta temperatura (37°C) e virulência em Cryptococcus neorformans |
| Beneficiário: | Marcelo Afonso Vallim |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |