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The role of heat shock proteins HsfA and Hsp90 and the regulator SmiA at cell wall integrity pathway activity in the opportunistic human pathogen Aspergillus fumigatus

Abstract

The cell wall is essential for the survival of the fungal cell and is also a protective element against environmental stresses preventing osmotic damage to the cell. The underlying mechanisms whereby the fungal cells build and remodel the cell wall under stressing conditions are of great relevance considering the high mortality rates caused by the human opportunistic fungal pathogen Aspergillus fumigatus. Our laboratory has focused on the investigation of the cell wall integrity pathway (CWI), the main signaling transduction pathway responsible for fungal cell wall synthesis. Previously, we identified the physical interaction between the molecular chaperone Hsp90 and different components of the CWI pathway, such as the apical protein kinase PkcA, the terminal MAP kinase MpkA and the main transcription factor of this pathway, RlmA which interaction may be direct or via the Hsp90-MpkA complex. Furthermore, we observed that the loss of function of the transcription factor HsfA, a key regulator of the heat shock response in different organisms, alters the activity of the CWI pathway indicating that there is a direct correlation between cell wall and temperature stresses. Our data also indicate that the CWI pathway in A. fumigatus acts in a coordinated manner alongside other signaling circuits and other regulatory proteins. Among these putative regulators is the SmiA gene, the Saccharomyces cerevisiae homolog SMI1, which is a member of the Pkc1-mediated signaling pathway. Thus, the aims of this project are (i) the identification of HsfA transcriptional targets related to the maintenance of cell wall integrity, (ii) large scale identification of the Hsp90 clientele focusing on proteins that might play a role in the maintenance or reinforcement of cell wall (iii) the molecular characterization of the SmiA gene and (iv) the evaluation of the interaction of SmiA with the CWI pathway components and with Hsp90. (AU)

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Scientific publications (9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROCHA, MARINA CAMPOS; TADINI MARILHANO FABRI, JOAO HENRIQUE; SILVA, LILIAN PEREIRA; FIGUEIREDO ANGOLINI, CELIO FERNANDO; BERTOLINI, MARIA CELIA; DA CUNHA, ANDERSON FERREIRA; VALIANTE, VITO; GOLDMAN, GUSTAVO HENRIQUE; FILL, TAICIA PACHECO; MALAVAZI, IRAN. Transcriptional Control of the Production of Aspergillus fumigatus Conidia-Borne Secondary Metabolite Fumiquinazoline C Important for Phagocytosis Protection. Genetics, v. 218, n. 1 MAY 2021. Web of Science Citations: 0.
FABRI, JOAO HENRIQUE TADINI MARILHANO; ROCHA, MARINA CAMPOS; FERNANDES, CAROLINE MOTA; PERSINOTI, GABRIELA FELIX; RIES, LAURE NICOLAS ANNICK; DA CUNHA, ANDERSON FERREIRA; GOLDMAN, GUSTAVO HENRIQUE; DEL POETA, MAURIZIO; MALAVAZI, IRAN. The Heat Shock Transcription Factor HsfA Is Essential for Thermotolerance and Regulates Cell Wall Integrity in Aspergillus fumigatus. FRONTIERS IN MICROBIOLOGY, v. 12, APR 9 2021. Web of Science Citations: 0.
ROCHA, MARINA CAMPOS; MINARI, KARINE; FABRI, JOAO HENRIQUE TADINI MARILHANO; KERKAERT, JOSHUA D.; GAVA, LISANDRA MARQUES; DA CUNHA, ANDERSON FERREIRA; CRAMER, ROBERT A.; BORGES, JULIO CESAR; MALAVAZI, IRAN. Aspergillus fumigatusHsp90 interacts with the main components of the cell wall integrity pathway and cooperates in heat shock and cell wall stress adaptation. Cellular Microbiology, v. 23, n. 2 FEB 2021. Web of Science Citations: 1.
FABRI, JOAO HENRIQUE TADINI MARILHANO; DE SA, NIVEA PEREIRA; MALAVAZI, IRAN; DEL POETA, MAURIZIO. The dynamics and role of sphingolipids in eukaryotic organisms upon thermal adaptation. PROGRESS IN LIPID RESEARCH, v. 80, NOV 2020. Web of Science Citations: 0.
CASTILHO DE ALMEIDA, NATALIA ELLEN; ESTEVES, FRANCIELE GREGO; APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; DE PAULA, CARLA PERES; DA CUNHA, ANDERSON FERREIRA; MALAVAZI, IRAN; PALMA, MARIO SERGIO; RODRIGUES-FILHO, EDSON. Digestion of Intact Gluten Proteins by Bifidobacterium Species: Reduction of Cytotoxicity and Proinflammatory Responses. Journal of Agricultural and Food Chemistry, v. 68, n. 15, p. 4485-4492, APR 15 2020. Web of Science Citations: 0.
ROCHA, MARINA CAMPOS; TADINI MARILHANO FABRI, JOAO HENRIQUE; SIMOES, ISABELLE TAIRA; SILVA-ROCHA, RAFAEL; HAGIWARA, DAISUKE; DA CUNHA, ANDERSON FERREIRA; GOLDMAN, GUSTAVO HENRIQUE; CANOVAS, DAVID; MALAVAZI, IRAN. The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus fumigatus Asexual Development. Applied and Environmental Microbiology, v. 86, n. 7 APR 2020. Web of Science Citations: 0.
FABRI, JOAO HENRIQUE T. M.; ROCHA, MARINA C.; MALAVAZI, IRAN. Overview of the Interplay Between Cell Wall Integrity Signaling Pathways and Membrane Lipid Biosynthesis in Fungi: Perspectives for Aspergillus fumigatus. CURRENT PROTEIN & PEPTIDE SCIENCE, v. 21, n. 3, p. 265-283, 2020. Web of Science Citations: 1.
TADINI MARILHANO FABRI, JOAO HENRIQUE; GODOY, NAIANE LIMA; ROCHA, MARINA CAMPOS; MUNSHI, MANSA; COCIO, TIAGO ALEXANDRE; VON ZESKA KRESS, MARCIA REGINA; FILL, TAICIA PACHECO; DA CUNHA, ANDERSON FERREIRA; DEL POETA, MAURIZIO; MALAVAZI, IRAN. The AGC Kinase YpkA Regulates Sphingolipids Biosynthesis and Physically Interacts With SakA MAP Kinase in Aspergillus fumigatus. FRONTIERS IN MICROBIOLOGY, v. 9, JAN 14 2019. Web of Science Citations: 1.
PIVA, ROGER H.; ROCHA, MARINA C.; PIVA, DIOGENES H.; IMASATO, HIDETAKE; MALAVAZI, IRAN; RODRIGUES-FILHO, UBIRAJARA P. Acidic Dressing Based on Agarose/Cs2.5H0.5PW12O40 Nanocomposite for Infection Control in Wound Care. ACS APPLIED MATERIALS & INTERFACES, v. 10, n. 37, p. 30963-30972, SEP 19 2018. Web of Science Citations: 3.

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