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The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence

Grant number: 16/07870-9
Support type:Research Projects - Thematic Grants
Duration: July 01, 2017 - June 30, 2022
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal researcher:Gustavo Henrique Goldman
Grantee:Gustavo Henrique Goldman
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Pesquisadores principais:
Iran Malavazi
Assoc. researchers: Agostinho Albérico Rodrigues de Carvalho
Associated grant(s):19/23231-4 - Characterizing the genomic and phenotypic diversity of clinical isolates from human fungal pathogens in the Aspergillus nidulans species complex, AP.R SPRINT
18/22040-8 - Fungal receptor-mediated glucose sensing regulates light-dependent development and toxin production, AP.R SPRINT
Associated scholarship(s):20/10536-9 - Organization and integration of large scale data to study the dynamics of expression of MAP kinases of the fungus Aspergillus fumigatus in diverse genetic and environmental conditions, BP.TT
19/10727-1 - Molecular characterization of a receptor coupled to a g protein (GPCR) of Aspergillus fumigatus, BP.MS
18/25217-6 - Organization and integration of large scale data to study the dynamics of expression of map kinases of the fungus Aspergillus fumigatus in diverse genetic and environmental conditions, BP.TT
+ associated scholarships 18/00715-3 - Molecular characterization of Aspergillus fumigatus transcription factors involved in calcium metabolism., BP.PD
17/19288-5 - Characterization of MAPKs dependent-phosphoproteomes of Aspergillus fumigatus under stress conditions, BP.PD
18/00315-5 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence, BP.PD
16/12948-7 - The role of mitogen-activated protein kinase (MPKA) MpkA in regulating gliotoxin production in Aspergillus fumigatus., BP.PD
14/24951-7 - Identification of targets regulated by Aspergillus fumigatus phosphatase PhzA, BP.PD
14/00789-6 - Functional characterization of Aspergillus nidulans phosphatases involved on glucose metabolism, BP.PD - associated scholarships

Abstract

MAP kinases and phosphatases are the main signaling pathways of tolerance to different kinds of stresses in eukaryotes. The multifactorial nature of A. fumigatus virulence and pathogenicity program in the mammalian host places the response to different kinds of stresses as one of the most important responses in the process of establishment of this organism as a pathogen. These signaling pathways are important for the cell wall biosynthesis and remodeling, responses to oxidative stress and antifungal drugs, biofilm formation and adhesion, and possibly other essential features not yet investigated such as, blood dissemination from the pulmonary epithelium and strategies of immunological evasion. The understanding of the metabolic nets that are coordinated by MAP kinases will provide an opportunity for the construction of the signaling pathways that are important for stress tolerance and the establishment of the A. fumigatus virulence and pathogenicity program in mammals. Thus, the main objectives of this project are: (i) the identification of specific transcription factors that are activated by different kinds of stress and that are dependent on MAP kinases; (ii) the identification of proteins that interact physically with the MAP kinases when A. fumigatus is exposed to different kinds of stresses; (iii) the investigation of a possible "crosstalk" among the different A. fumigatus MAP kinases during different kinds of stresses; (iv) the molecular characterization of MpkB and the verification if this MAP kinase is important for A. fumigatus virulence, and (v) the characterization of the interaction between the A. fumigatus mutants generated in this study and the immunosupressed and imunocompetent murine hosts. (AU)

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Scientific publications (34)
(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)
MANFIOLLI, ADRIANA OLIVEIRA; MATTOS, ELICIANE CEVOLANI; DE ASSIS, LEANDRO JOSE; SILVA, LILIAN PEREIRA; ULAS, MEVLUT; BROWN, NEIL ANDREW; SILVA-ROCHA, RAFAEL; BAYRAM, OZGUR; GOLDMAN, GUSTAVO H.. Aspergillus fumigatus High Osmolarity Glycerol Mitogen Activated Protein Kinases SakA and MpkC Physically Interact During Osmotic and Cell Wall Stresses. FRONTIERS IN MICROBIOLOGY, v. 10, . (16/07870-9, 14/00789-6, 17/19288-5)
ROKAS, ANTONIS; MEAD, MATTHEW E.; STEENWYK, JACOB L.; OBERLIES, NICHOLAS H.; GOLDMAN, GUSTAVO H.. Evolving moldy murderers: Aspergillus section Fumigati as a model for studying the repeated evolution of fungal pathogenicity. PLOS PATHOGENS, v. 16, n. 2, . (16/07870-9)
BASTOS, RAFAEL W.; ROSSATO, LUANA; GOLDMAN, GUSTAVO H.; SANTOS, DANIEL A.. ungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyon. PLOS PATHOGENS, v. 17, n. 12, . (16/07870-9, 17/19821-5, 18/10962-8)
KNOWLES, SONJA L.; MEAD, MATTHEW E.; SILVA, LILIAN PEREIRA; RAJA, HUZEFA A.; STEENWYK, JACOB L.; GOLDMAN, GUSTAVO H.; OBERLIES, NICHOLAS H.; ROKAS, ANTONIS. Gliotoxin, a Known Virulence Factor in the Major Human Pathogen Aspergillus fumigatus, Is Also Biosynthesized by Its Nonpathogenic Relative Aspergillus fischeri. MBIO, v. 11, n. 1, . (16/21392-2, 16/07870-9)
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, . (16/07870-9, 15/17541-0, 17/19694-3)
MEAD, MATTHEW E.; STEENWYK, JACOB L.; SILVA, LILIAN P.; DE CASTRO, PATRICIA A.; SAEED, NAUMAN; HILLMANN, FALK; GOLDMAN, GUSTAVO H.; ROKAS, ANTONIS. An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely related Aspergillus fungi. Genetics, v. 218, n. 2, . (16/07870-9)
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, . (16/07870-9, 17/19694-3, 15/17541-0)
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, . (17/19694-3, 16/07870-9)
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, . (17/19694-3, 16/07870-9)
BASTOS, RAFAEL WESLEY; ROSSATO, LUANA; VALERO, CLARA; LAGROU, KATRIEN; COLOMBO, ARNALDO LOPES; GOLDMAN, GUSTAVO H.. Potential of Gallium as an Antifungal Agent. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, . (16/07870-9, 17/02203-7, 17/19095-2)
DE ASSIS, LEANDRO JOSE; SILVA, LILIAN PEREIRA; LIU, LI; SCHMITT, KERSTIN; VALERIUS, OLIVER; BRAUS, GERHARD H.; ANNICK RIES, LAURE NICOLAS; GOLDMAN, GUSTAVO HENRIQUE. The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi. PLOS GENETICS, v. 16, n. 8, . (14/00789-6, 16/07870-9, 17/23624-0)
DROTT, M. T.; BASTOS, R. W.; ROKAS, A.; RIES, L. N. A.; GABALDON, T.; GOLDMAN, G. H.; KELLER, N. P.; GRECO, C.. Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates. MSPHERE, v. 5, n. 2, . (17/14159-2, 17/19821-5, 19/00631-7, 16/07870-9)
DOS SANTOS, RENATO A. C.; STEENWYK, JACOB L.; RIVERO-MENENDEZ, OLGA; MEAD, MATTHEW E.; SILVA, LILIAN P.; BASTOS, RAFAEL W.; ALASTRUEY-LZQUIERDO, ANA; GOLDMAN, GUSTAVO H.; ROKAS, ANTONIS. Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis. FRONTIERS IN GENETICS, v. 11, . (17/21983-3, 16/07870-9)
DOS REIS, THAILA FERNANDA; CRIVELENTE HORTA, MARIA AUGUSTA; COLABARDINI, ANA CRISTINA; FERNANDES, CAROLINE MOTA; SILVA, LILIAN PEREIRA; BASTOS, RAFAEL WESLEY; DE LAZARI FONSECA, MARIA VITORIA; WANG, FANG; MARTINS, CELSO; RODRIGUES, MARCIO L.; et al. Screening of Chemical Libraries for New Antifungal Drugs against Aspergillus fumigatus Reveals Sphingolipids Are Involved in the Mechanism of Action of Miltefosine. MBIO, v. 12, n. 4, . (16/07870-9, 16/12948-7)
COLABARDINI, ANA CRISTINA; WANG, FANG; DONG, ZHIQIANG; PARDESHI, LAKHANSING; ROCHA, MARINA CAMPOS; COSTA, JONAS HENRIQUE; DOS REIS, THAILA FERNANDA; BROWN, ALEC; JABER, QAIS Z.; FRIDMAN, MICHA; et al. eterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungi. Genetics, v. 220, n. 1, . (18/00315-5, 17/07536-4, 17/19694-3, 16/07870-9)
DE CASTRO, PATRICIA ALVES; COLABARDINI, ANA CRISTINA; MANFIOLLI, ADRIANA OLIVEIRA; CHIARATTO, JESSICA; SILVA, LILIAN PEREIRA; MATTOS, ELICIANE CEVOLANI; PALMISANO, GIUSEPPE; ALMEIDA, FAUSTO; PERSINOTI, GABRIELA FELIX; ANNICK RIES, LAURE NICOLAS; et al. Aspergillus fumigatus calcium-responsive transcription factors regulate cell wall architecture promoting stress tolerance, virulence and caspofungin resistance. PLOS GENETICS, v. 15, n. 12, . (17/07536-4, 16/21392-2, 14/06863-3, 16/12948-7, 16/07870-9, 16/22062-6, 14/04783-2, 17/19288-5)
JOHNS, LOUISE E.; GOLDMAN, GUSTAVO H.; RIES, LAURE N. A.; BROWN, NEIL A.. Nutrient sensing and acquisition in fungi: mechanisms promoting pathogenesis in plant and human hosts. FUNGAL BIOLOGY REVIEWS, v. 36, p. 1-14, . (16/07870-9, 17/14159-2, 18/22040-8)
STEENWYK, JACOB L.; LIND, ABIGAIL L.; RIES, LAURE N. A.; DOS REIS, THAILA F.; SILVA, LILIAN P.; ALMEIDA, FAUSTO; BASTOS, RAFAEL W.; FRAGA DA SILVA, THAIS FERNANDA DE CAMPOS; BONATO, VANIA L. D.; PESSONI, ANDRE MOREIRA; et al. Pathogenic Allodiploid Hybrids of Aspergillus Fungi. Current Biology, v. 30, n. 13, p. 2495+, . (17/14159-2, 16/03322-7, 16/07870-9)
BASTOS, RAFAEL WESLEY; VALERO, CLARA; SILVA, LILIAN PEREIRA; SCHOEN, TAYLOR; DROTT, MILTON; BRAUER, VERONICA; SILVA-ROCHA, RAFAEL; LIND, ABIGAIL; STEENWYK, JACOB L.; ROKAS, ANTONIS; et al. Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen Aspergillus nidulans. MSPHERE, v. 5, n. 2, . (16/07870-9, 18/14762-3, 17/19821-5, 17/14159-2, 19/00631-7)
ANNICK RIES, LAURE NICOLAS; DE CASTRO, PATRICIA ALVES; SILVA, LILIAN PEREIRA; VALERO, CLARA; DOS REIS, THAILA FERNANDA; SABORANO, RAQUEL; DUARTE, IOLA F.; PERSINOTI, GABRIELA FELIX; STEENWYK, JACOB L.; ROKAS, ANTONIS; et al. spergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicit. MBIO, v. 12, n. 4, . (16/07870-9, 18/00715-3, 16/12948-7, 17/08750-0, 17/14159-2)
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, . (16/07870-9, 15/17541-0, 17/19694-3, 17/26131-5, 17/07335-9, 14/07206-6)
DE ASSIS, LEANDRO JOSE; SILVA, LILIAN PEREIRA; BAYRAM, OZGUR; DOWLING, PAUL; KNIEMEYER, OLAF; KRUEGER, THOMAS; BRAKHAGE, AXEL A.; CHEN, YINGYING; DONG, LIGUO; TAN, KAELING; et al. Carbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreA. MBIO, v. 12, n. 1, . (16/03900-0, 16/07870-9, 14/00789-6, 17/14159-2)
DE CASTRO, PATRICIA ALVES; VALERO, CLARA; CHIARATTO, JESSICA; COLABARDINI, ANA CRISTINA; PARDESHI, LAKHANSING; SILVA, LILIAN PEREIRA; ALMEIDA, FAUSTO; ROCHA, MARINA CAMPOS; SILVA, ROBERTO NASCIMENTO; MALAVAZI, IRAN; et al. Novel Biological Functions of the NsdC Transcription Factor in Aspergillus fumigatus. MBIO, v. 12, n. 1, . (16/07870-9, 18/00715-3, 16/21392-2, 17/07536-4, 16/22062-6, 16/12948-7, 19/10097-8)
RIES, LAURE N. A.; PARDESHI, LAKHANSING; DONG, ZHICLIANG; TAN, KAELING; STEENWYK, JACOB L.; COLABARDINI, ANA CRISTINA; FERREIRA FILHO, JAIRE A.; DE CASTRO, PATRICIA A.; SILVA, LILIAN P.; PREITE, NYCOLAS W.; et al. The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLOS PATHOGENS, v. 16, n. 7, . (17/14159-2, 17/21983-3, 18/25217-6, 17/07536-4, 17/01188-4, 13/50954-0, 14/00789-6, 13/07937-8, 16/07870-9, 19/09278-8, 16/03322-7)
MANFIOLLI, ADRIANA OLIVEIRA; SIQUEIRA, FILIPE SILVA; DOS REIS, THAILA FERNANDA; VAN DIJCK, PATRICK; SCHREVENS, SANNE; HOEFGEN, SANDRA; FOEGE, MARTIN; STRASSBURGER, MARIA; DE ASSIS, LEANDRO JOSE; HEINEKAMP, THORSTEN; et al. Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in Aspergillus fumigatus. MBIO, v. 10, n. 2, . (14/24951-7, 14/00789-6, 16/07870-9)
ANNICK RIES, LAURE NICOLAS; BEATTIE, SARAH; CRAMER, ROBERT A.; GOLDMAN, GUSTAVO H.. Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi. Molecular Microbiology, v. 107, n. 3, p. 277-297, . (16/07870-9)
ANNICK RIES, LAURE NICOLAS; DE ASSIS, LEANDRO JOSE; SANTOS RODRIGUES, FERNANDO JOSE; CALDANA, CAMILA; ROCHA, MARINA CAMPOS; MALAVAZI, IRAN; BAYRAM, OZGUR; GOLDMAN, GUSTAVO H.. The Aspergillus nidulans Pyruvate Dehydrogenase Kinases Are Essential To Integrate Carbon Source Metabolism. G3-GENES, GENOMES, GENETICS, v. 8, n. 7, p. 2445-2463, . (16/07870-9, 14/00789-6)
STEENWYK, JACOB L.; MEAD, MATTHEW E.; KNOWLES, SONJA L.; RAJA, HUZEFA A.; ROBERTS, CHRISTOPHER D.; BADER, OLIVER; HOUBRAKEN, JOS; GOLDMAN, GUSTAVO H.; OBERLIES, NICHOLAS H.; ROKAS, ANTONIS. Variation Among Biosynthetic Gene Clusters, Secondary Metabolite Profiles, and Cards of Virulence AcrossAspergillusSpecies. Genetics, v. 216, n. 2, p. 481-497, . (16/07870-9)
CORREA DOS SANTOS, RENATO AUGUSTO; RIVERO-MENENDEZ, OLGA; STEENWYK, JACOB L.; MEAD, MATTHEW E.; GOLDMAN, GUSTAVO HENRIQUE; ALASTRUEY-IZQUIERDO, ANA; ROKAS, ANTONIS. Draft Genome Sequences of Four Aspergillus Section Fumigati Clinical Strains. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 9, n. 40, . (17/21983-3, 16/07870-9, 19/07526-4)
SILVA, LILIAN PEREIRA; FRAWLEY, DEAN; DE ASSIS, LEANDRO JOSE; TIERNEY, CIARA; FLEMING, ALASTAIR B.; BAYRAM, OZGUR; GOLDMAN, GUSTAVO HENRIQUE. Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources. MSPHERE, v. 5, n. 5, . (16/07870-9, 14/00789-6, 16/21392-2)
DA COSTA FILHO, AILTON PEREIRA; PEREIRA BRANCINI, GUILHERME THOMAZ; DE CASTRO, PATRICIA ALVES; VALERO, CLARA; FERREIRA FILHO, JAIRE ALVES; SILVA, LILIAN PEREIRA; ROCHA, MARINA CAMPOS; MALAVAZI, IRAN; DE MORAES PONTES, JOAO GUILHERME; FILL, TAICIA; et al. Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence. MBIO, v. 11, n. 5, . (16/07870-9, 18/00715-3, 16/12948-7, 19/11929-7, 18/25217-6, 19/10727-1, 16/21392-2, 17/14159-2, 19/06359-7, 18/10962-8)
DE ASSIS, LEANDRO JOSE; ULAS, MEVLUT; ANNICK RIES, LAURE NICOLAS; EL RAMLI, NADIA ALI MOHAMED; SARIKAYA-BAYRAM, OZLEM; BRAUS, GERHARD H.; BAYRAM, OZGUR; GOLDMAN, GUSTAVO HENRIQUE. Regulation of Aspergillus nidulans CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47. MBIO, v. 9, n. 3, . (16/07870-9, 14/00789-6, 16/03900-0)
MATTOS, ELICIANE CEVOLANI; SILVA, LILIAN PEREIRA; VALERO, CLARA; DE CASTRO, PATRICIA ALVES; DOS REIS, THAILA FERNANDA; RIBEIRO, LILIANE F. C.; MARTEN, MARK R.; SILVA-ROCHA, RAFAEL; WESTMANN, CAUA; TOMICH DE PAULA DA SILVA, CARLOS HENRIQUE; et al. The Aspergillus fumigatus Phosphoproteome Reveals Roles of High-Osmolarity Glycerol Mitogen-Activated Protein Kinases in Promoting Cell Wall Damage and Caspofungin Tolerance. MBIO, v. 11, n. 1, . (18/18043-1, 16/07870-9, 17/19288-5)
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, . (16/07870-9, 15/17541-0, 17/19694-3)

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