Characterization of transcription factors of Aspergillus fumigatus important for responses to different stresses

Author(s)

Jéssica Chiaratto

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2019-03-21

Examining board members

Gustavo Henrique Goldman; Iran Malavazi; Laure Nicolas Annick Ries; Roberto do Nascimento Silva

• Advisor: Gustavo Henrique Goldman

Abstract

Aspergillus fumigatus is a saprophytic fungus and one of the main human pathogenic fungi. Their conidia are inhaled and reach the lungs, where they activate and germinate, and can trigger aspergillosis. Aspergillosis clinical forms presents great risk, mainly for the immunosuppressed patients. Calcium signaling has important role in physiological responses. Calcium corresponds to a secondary messenger that participates in different biological processes, such as cell cycle, differentiation, or homeostasis. In addition, echinocandins, such as caspofungin, are antifungal drugs that target the fungal cell wall. These agents reduce the total concentration of 1,3-?- D-glucans on the cell wall, by inhibiting the activity of 1,3-?-glucan synthase. Inhibition of the synthesis of cell wall components through antifungal drugs may be an important target against infections caused by A. fumigatus. Screening of transcription factors genes have been identified. The deletion of the nsdC gene results from increased sensitivity to CaCl2, EGTA, Congo Red, Nikkomycin Z, Calcofluor White, Caspofungin (reduced paradoxical effect), 44C, Menadione and Tbutyl hydroperoxide. In addition, the ?nsdC null mutant is more resistant to Sorbitol and Cyclosporin. The transcription factor NsdC seems to be involved in the signaling of calcium, and its expression is altered in the absence of the CrzA transcription factor. In addition, NsdC has been shown to be important in processes related to the cell wall, since its deletion leads to the formation of more branched and disorganized hyphae and thicker cell wall. This transcription factor also appears to be a repressor of asexual reproduction. This is due to the fact that the null mutant ?nsdC produces conidia in liquid medium and leads to a significant increase in the expression of brlA. In addition, the NsdC protein is mostly present in the nucleus, after treatment with CaCl2. Other mutants of transcription factors sensitivity to Caspofungin have been identified: ?cbfA, ?nctA, ?nctB and ?nctC. Some evidence indicates that NctA and NctB are part of the same complex. Besides that, NctC seems to be related to temperature and osmotic stresses, being important for virulence in A. fumigatus. Therefore, more studies are needed in order to better understand the roles of these genes and may be important in bringing greater information about potential therapeutic targets in the treatment of aspergillosis. (AU)

• FAPESP's process: 16/22062-6 - Molecular characterization of htlA and fhdA transcription factors of human pathogenic fungus Aspergillus fumigatus
• Grantee: Jéssica Chiaratto
• Support Opportunities: Scholarships in Brazil - Master