Molecular characterization of mechanisms involved in pathogenicity and cell signaling in fungi

• Grant number: 14/03847-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2015
• End date: April 30, 2020
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Nilce Maria Martinez-Rossi
• Grantee: Nilce Maria Martinez-Rossi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Antonio Rossi Filho
• Associated researchers: Elza Akie Sakamoto Lang ; Gabriela Felix Persinoti ; Nalu Teixeira de Aguiar Peres ; Rafael Silva Rocha
• Associated scholarship(s): 18/15458-6 - Alternative splicing in genes coding for HSPs as a response to antifungals in the dermatophyte Trichophyton rubrum, BP.IC; 18/11319-1 - Transcription factors and cell signaling., BP.PD; 16/04274-6 - Transcription factors and cell signaling, BP.PD; 15/23435-8 - Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors, BP.PD

Abstract

Dermatophytes are filamentous fungi that use keratin as a nutrient source during infection of skin, nail and hair. Dermatophyte adherence and secretion of enzymes are key factors in the colonization of the host tissues, which can be regulated in response to phosphate levels, different carbon and nitrogen sources, and ambient pH. Dermatophytoses constitute one of the most common fungal infections. Despite its clinical importance, the molecular aspects concerning colonization, influence of various environmental factors, gene regulation of enzyme secretion, and drug resistance are not yet fully elucidated. The main goal of this proposal is the understanding of mechanisms used by dermatophytes, especially Trichophyton rubrum, during the colonization of the host tissue, and the signaling pathways involved in sensing, and in transduction of molecular signals in response to the environment. It is intended to assess the relationship between alternative splicing events and response to cytotoxic drugs; to identify genes and non-coding RNAs potentially involved in the pathogenicity of dermatophytes, and to understand the molecular mechanisms involved in sensing and modulation of gene expression that allow fungi to survive under stressful environments, such as extremes of pH, nutrient deprivation, and interaction with host molecules in vitro. Thus, it is expected to reveal molecular mechanisms involved in gene expression regulation, as well as alternative forms of regulation involving ncRNA and mRNA isoforms required for dermatophytes adaptation to adverse environmental conditions such as antifungal drugs and interaction with the host as well as the relationship between different signaling and metabolic pathways that allow the survival of fungi under such conditions. (AU)

Scientific publications

(25)

(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)

BITENCOURT, TAMIRES APARECIDA; REZENDE, CAROLINE PATINI; QUARESEMIN, NATALIA RENAULT; MORENO, PEDRO; HATANAKA, OTAVIO; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE MARIA; ALMEIDA, FAUSTO. Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions. FRONTIERS IN IMMUNOLOGY, v. 9, OCT 9 2018. (14/03847-7, 16/15055-3, 15/23435-8, 16/03322-7)

MARTINS, MAIRA POMPEU; ROSSI, ANTONIO; SANCHES, PABLO RODRIGO; BORTOLOSSI, JULIO CESAR; MARTINEZ-ROSSI, NILCE MARIA. Comprehensive analysis of the dermatophyte Trichophyton rubrum transcriptional profile reveals dynamic metabolic modulation. Biochemical Journal, v. 477, n. 5, p. 873-885, MAR 2020. (18/11319-1, 14/03847-7)

BITENCOURT, TAMIRES A.; LANG, ELZA A. S.; SANCHES, PABLO R.; PERES, NALU T. A.; OLIVEIRA, VANDERCI M.; FACHIN, ANA LUCIA; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. HacA Governs Virulence Traits and Adaptive Stress Responses in Trichophyton rubrum. FRONTIERS IN MICROBIOLOGY, v. 11, FEB 20 2020. (15/23435-8, 14/03847-7)

MARTINS, MAIRA P.; GOMES, ERISTON V.; SANCHES, PABLO R.; PEDERSOLI, WELLINGTON R.; MARTINEZ-ROSSI, NILCE M.; ROSSI, ANTONIO. mus-52 disruption and metabolic regulation in Neurospora crassa: Transcriptional responses to extracellular phosphate availability. PLoS One, v. 13, n. 4, APR 18 2018. (16/04274-6, 14/03847-7)

MENDES, NIEGE S.; BITENCOURT, TAMIRES A.; SANCHES, PABLO R.; SILVA-ROCHA, RAFAEL; MARTINEZ-ROSSI, NILCE M.; ROSSI, ANTONIO. Transcriptome-wide survey of gene expression changes and alternative splicing in Trichophyton rubrum in response to undecanoic acid. SCIENTIFIC REPORTS, v. 8, FEB 6 2018. (14/03847-7, 15/23435-8)

MENDES, NIEGE S.; SILVA, PATRICIA M.; SILVA-ROCHA, RAFAEL; MARTINEZ-ROSSI, NILCE M.; ROSSI, ANTONIO. Pre-mRNA splicing is modulated by antifungal drugs in the filamentous fungus Neurospora crassa. FEBS OPEN BIO, v. 6, n. 4, p. 358-368, APR 2016. (14/03847-7)

SANTOS, HEMELIN L.; LANG, ELZA A. S.; SEGATO, FERNANDO; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Terbinafine resistance conferred by multiple copies of the salicylate 1-monooxygenase gene in Trichophyton rubrum. Medical Mycology, v. 56, n. 3, p. 378-381, APR 2018. (08/58634-7, 14/03847-7)

DA SILVA, LARISSA GOMES; MARTINS, MAIRA POMPEU; SANCHES, PABLO RODRIGO; DE AGUIAR PERES, NALU TEIXEIRA; MARTINEZ-ROSSI, NILCE MARIA; ROSSI, ANTONIO. Saline stress affects the pH-dependent regulation of the transcription factor PacC in the dermatophyteTrichophyton interdigitale. Brazilian Journal of Microbiology, v. 51, n. 4, JUN 2020. (09/08411-4, 10/15017-8, 14/03847-7, 18/11319-1)

MARTINS, MAIRA POMPEU; CAPOVILLA FRANCESCHINI, ANA CAROLINA; JACOB, TIAGO RINALDI; ROSSI, ANTONIO; MARIA MARTINEZ-ROSSI, NILCE. Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes. Journal of Medical Microbiology, v. 65, p. 6-pg., 2016-07-01. (14/03847-7)

MARTINEZ-ROSSI, NILCE M.; PERES, NALU T. A.; ROSSI, ANTONIO. Pathogenesis of Dermatophytosis: Sensing the Host Tissue. Mycopathologia, v. 182, n. 1-2, p. 13-pg., 2017-02-01. (14/03847-7)

BITENCOURT, T. A.; MENDES, N. S.; SANCHES, P. R.; ROSSI, A.; MARTINEZ-ROSSI, N. M.. Undecanoic acid toxicity toward Trichophyton rubrum relies on an oxidative stress status. Medical Mycology, v. 56, p. 1-pg., 2018-06-01. (14/03847-7, 15/23435-8)

GOMES, ERISTON V.; BORTOLOSSI, JULIO C.; SANCHES, PABLO R.; MENDES, NIEGE S.; MARTINEZ-ROSSI, NILCE M.; ROSSI, ANTONIO. STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 11, NOV 2018. (14/03847-7, 16/04274-6)

MARTINEZ-ROSSI, NILCE M.; PERES, NALU T. A.; ROSSI, ANTONIO. Pathogenesis of Dermatophytosis: Sensing the Host Tissue. Mycopathologia, v. 182, n. 1-2, SI, p. 215-227, FEB 2017. (14/03847-7)

MARTINS, MAIRA POMPEU; CAPOVILLA FRANCESCHINI, ANA CAROLINA; JACOB, TIAGO RINALDI; ROSSI, ANTONIO; MARIA MARTINEZ-ROSSI, NILCE. Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes. Journal of Medical Microbiology, v. 65, n. 7, p. 605-610, JUL 2016. (14/03847-7)

MARTINS, MAIRA P.; SILVA, LARISSA G.; ROSSI, ANTONIO; SANCHES, PABLO R.; SOUZA, LARISSA D. R.; MARTINEZ-ROSSI, NILCE M.. Global Analysis of Cell Wall Genes Revealed Putative Virulence Factors in the Dermatophyte Trichophyton rubrum. FRONTIERS IN MICROBIOLOGY, v. 10, SEP 19 2019. (10/15017-8, 14/03847-7, 18/11319-1)

JACOB, TIAGOR.; PERES, NALUT. A.; MARTINS, MAIRA P.; LANG, ELZA. S.; SANCHES, PABLO R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Heat Shock Protein 90 (Hsp90) as a Molecular Target for the Development of Novel Drugs Against the Dermatophyte Trichophyton rubrum. FRONTIERS IN MICROBIOLOGY, v. 6, NOV 10 2015. (14/03847-7, 09/08411-4)

DE AGUIAR PERES, NALU TEIXEIRA; DA SILVA, LARISSA GOMES; SANTOS, RODRIGO DA SILVA; JACOB, TIAGO RINALDI; PERSINOTI, GABRIELA FELIX; ROCHA, LENALDO BRANCO; FALCAO, JULIANA PFRIMER; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE MARIA. In vitro and ex vivo infection models help assess the molecular aspects of the interaction of Trichophyton rubrum with the host milieu. Medical Mycology, v. 54, n. 4, p. 420-427, MAY 2016. (14/03847-7, 09/08411-4)

BITENCOURT, TAMIRES A.; OLIVEIRA, FELIPE B.; SANCHES, PABLO R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. The prp4 kinase gene and related spliceosome factor genes in Trichophyton rubrum respond to nutrients and antifungals. Journal of Medical Microbiology, v. 68, n. 4, p. 591-599, APR 2019. (14/03847-7, 15/23435-8)

PEDERSOLI, WELLINGTON RAMOS; SANTOS, RODRIGO DA SILVA; VIEIRA NOGUEIRA, KAROLINE MARIA; SILVA-ROCHA, RAFAEL; ROSSI, ANTONIO. Deletion of pH Regulator pac-3 Affects Cellulase and Xylanase Activity during Sugarcane Bagasse Degradation by Neurospora crassa. PLoS One, v. 12, n. 1, JAN 20 2017. (14/09493-2, 14/03847-7)

MARTINS, MAIRA POMPEU; MARTINEZ-ROSSI, NILCE M.; SANCHES, PABLO R.; GOMES, ERISTON VIEIRA; BERTOLINI, MARIA CELIA; PEDERSOLI, WELLINGTON R.; SILVA, ROBERTO NASCIMENTO; ROSSI, ANTONIO. The pH Signaling Transcription Factor PAC-3 Regulates Metabolic and Developmental Processes in Pathogenic Fungi. FRONTIERS IN MICROBIOLOGY, v. 10, SEP 4 2019. (16/04274-6, 18/11319-1, 14/03847-7)

MAÍRA POMPEU MARTINS; NILCE MARIA MARTINEZ-ROSSI; PABLO RODRIGO SANCHES; ANTONIO ROSSI. The PAC-3 transcription factor critically regulates phenotype-associated genes in Neurospora crassa. GENETICS AND MOLECULAR BIOLOGY, v. 43, n. 3, 2020-06-22. (18/11319-1, 14/03847-7)

NEVES-DA-ROCHA, JOAO; BITENCOURT, TAMIRES A.; DE OLIVEIRA, VANDERCI M.; SANCHES, PABLO R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum. CELLS, v. 8, n. 10, OCT 2019. (15/23435-8, 14/03847-7, 18/15458-6)

MARTINEZ-ROSSI, NILCE M.; BITENCOURT, TAMIRES A.; PERES, NALU T. A.; LANG, ELZA A. S.; GOMES, ERISTON V.; QUARESEMIN, NATALIA R.; MARTINS, MAIRA P.; LOPES, LUCIA; ROSSI, ANTONIO. Dermatophyte Resistance to Antifungal Drugs: Mechanisms and Prospectus. FRONTIERS IN MICROBIOLOGY, v. 9, MAY 29 2018. (16/04274-6, 14/03847-7, 15/23435-8)

MARTINEZ-ROSSI, NILCE M.; JACOB, TIAGO R.; SANCHES, PABLO R.; PERES, NALU T. A.; LANG, ELZA A. S.; MARTINS, MAIRA P.; ROSSI, ANTONIO. Heat Shock Proteins in Dermatophytes: Current Advances and Perspectives. CURRENT GENOMICS, v. 17, n. 2, p. 99-111, 2016. (14/03847-7, 09/08411-4)

GOMES, ERISTON V.; BORTOLOSSI, JULIO C.; SANCHES, PABLO R.; MENDES, NIEGE S.; MARTINEZ-ROSSI, NILCE M.; ROSSI, ANTONIO. STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 11, p. 11-pg., 2018-11-01. (14/03847-7, 16/04274-6)