Molecular mechanisms associated with pathogenicity and resistance in fungi: strategies for treating dermatophytosis

• Grant number: 19/22596-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2020
• End date: April 30, 2026
• 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
• City of the host institution: Ribeirão Preto
• Principal investigators: Antonio Rossi Filho
• Associated researchers: Fausto Bruno dos Reis Almeida ; Pablo Rodrigo Sanches
• Associated scholarship(s): 24/17493-4 - Transcription factors and cellular signaling pathways in pathogenicity and modulation of the immune response, BP.PD; 24/03135-9 - Prion Proteins and HSPs Involved in Controlling the Stress Response in Trichophyton rubrum., BP.MS; 22/15282-0 - Alternative splicing in HSPs coding genes related to pathogenicity of dermatophyte Trichophyton rubrum, BP.IC; + associated scholarships 21/10359-2 - Comparative systematic analysis of transcriptomes in the elucidation of potential antifungal targets, BP.PD; 21/10255-2 - Transcription factors and cell signaling pathways in pathogenicity and modulation of immune response, BP.PD; 21/04263-2 - Integrated proteostasis and cell signaling circuits for the control of the stress response in fungi, BP.DD - associated scholarships

Abstract

Dermatophyte Trichophyton rubrum is the pathogenic fungus with the highest incidence in clinical cases of superficial mycoses in human skin and nails. Although these infections are widespread, the mechanisms associated with successful pathogen-host interaction and drug resistance factors remain misunderstood. Considerable research efforts are being undertaken, aiming at the control of infections caused by dermatophyte fungi. Which is looking for possible cellular targets that will be useful in the development of new drugs with antifungal activity. Therefore, the identification of factors involved in pathogenicity and evaluation of specific genes and modulated metabolic pathways during the infectious process are crucial. Thus, the objectives of this project are: (1) the elucidation of cellular signaling pathways regulated by StuA, Ap1, PacC, and HacA transcription factors during interaction with the host; (2) identification of factors associated with innate immune response modulation during pathogen-host interaction; (3) comparative systematic analysis of transcriptomes, aiming to identify enzymes crucial for the metabolism and adaptation of fungi to different cultivation conditions; (4) identification of possible molecular targets for antifungal development; and (5) explore and validate strategies for the treatment of dermatophytosis. Thus, we aim to contribute to a better understanding thereof the relationships established between this clinically meaningful fungus and the human host, as well as to seek viable and efficient alternatives for the treatment of dermatophytosis. (AU)

Scientific publications

(15)

(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 A.; NEVES-DA-ROCHA, JOAO; MARTINS, MAIRA P.; SANCHES, PABLO R.; LANG, ELZA A. S.; BORTOLOSSI, JULIO C.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. StuA-Regulated Processes in the Dermatophyte Trichophyton rubrum: Transcription Profile, Cell-Cell Adhesion, and Immunomodulation. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUN 8 2021. (18/15458-6, 15/23435-8, 18/11319-1, 19/22596-9)

MARTINEZ-ROSSI, NILCE M.; PERES, NALU T. A.; BITENCOURT, TAMIRES A.; MARTINS, MAIRA P.; ROSSI, ANTONIO. State-of-the-Art Dermatophyte Infections: Epidemiology Aspects, Pathophysiology, and Resistance Mechanisms. JOURNAL OF FUNGI, v. 7, n. 8, AUG 2021. (15/23435-8, 18/11319-1, 19/22596-9)

MARTINS-SANTANA, LEONARDO; REZENDE, CAROLINE PATINI; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE MARIA; ALMEIDA, FAUSTO. Addressing Microbial Resistance Worldwide: Challenges over Controlling Life-Threatening Fungal Infections. PATHOGENS, v. 12, n. 2, p. 15-pg., 2023-02-01. (21/06794-5, 19/22596-9, 21/10255-2, 20/03215-1)

ROCHA, CARLOS H. LOPES; ROCHA, FLAVIANE M. GALVAO; BITENCOURT, TAMIRES A.; MARTINS, MAIRA P.; SANCHES, PABLO R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Synergism between the Antidepressant Sertraline and Caspofungin as an Approach to Minimise the Virulence and Resistance in the Dermatophyte Trichophyton rubrum. JOURNAL OF FUNGI, v. 8, n. 8, p. 13-pg., 2022-08-01. (18/11319-1, 15/23435-8, 19/22596-9)

LANG, ELZA A. S.; BITENCOURT, TAMIRES A.; PERES, NALU T. A.; LOPES, LUCIA; SILVA, LARISSA G.; CAZZANIGA, RODRIGO A.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. The stuA gene controls development, adaptation, stress tolerance, and virulence of the dermatophyte Trichophyton rubrum. MICROBIOLOGICAL RESEARCH, v. 241, DEC 2020. (15/23435-8, 19/22596-9, 09/08411-4, 10/15017-8)

NEVES-DA-ROCHA, JOAO; SANTOS-SABOYA, MARIA J.; LOPES, MARCOS E. R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections. MICROORGANISMS, v. 11, n. 8, p. 25-pg., 2023-08-01. (21/04263-2, 19/22596-9, 22/15282-0)

LOPES, MARCOS E. RAMOS; NEVES-DA-ROCHA, JOAO; SANCHES, PABLO R.; OLIVEIRA, VANDERCI M.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Alternative splicing is a driving force that tunes metabolic adaptations to virulence traits in the dermatophyte Trichophyton rubrum. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 15, p. 12-pg., 2025-09-10. (19/22596-9, 21/04263-2)

PETRUCELLI, MONISE FAZOLIN; MARTINS-SANTANA, LEONARDO; OLIVEIRA, VANDERCI M.; SANCHES, PABLO R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. The Transcription Factor StuA Regulates Oxidative Stress-Responsive Genes in Trichophyton rubrum. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 23, p. 16-pg., 2024-12-01. (21/10359-2, 19/22596-9, 21/10255-2)

ROCHA, CARLOS H. LOPES; ROCHA, FLAVIANE M. GALVAO; SANCHES, PABLO R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis. GENES, v. 16, n. 2, p. 11-pg., 2025-02-01. (19/22596-9)

BITENCOURT, TAMIRES A.; HATANAKA, OTAVIO; PESSONI, ANDRE M.; FREITAS, MATEUS S.; TRENTIN, GABRIEL; SANTOS, PATRICK; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.; ALVES, LYSANGELA L.; CASADEVALL, ARTURO; et al. Fungal Extracellular Vesicles Are Involved in Intraspecies Intracellular Communication. MBIO, v. 13, n. 1, p. 14-pg., 2022-01-01. (19/02504-2, 19/22596-9, 16/03322-7, 19/22454-0)

PERES, NALU T. A.; LANG, ELZA A. S.; BITENCOURT, TAMIRES A.; OLIVEIRA, VANDERCI M.; FACHIN, ANA LUCIA; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. The bZIP Ap1 transcription factor is a negative regulator of virulence attributes of the anthropophilic dermatophyte Trichophyton rubrum. CURRENT RESEARCH IN MICROBIAL SCIENCES, v. 3, p. 11-pg., 2022-01-01. (15/23435-8, 09/08411-4, 19/22596-9)

ROSSI, ANTONIO; MARTINS, MAIRA P.; BITENCOURT, TAMIRES A.; PERES, NALU T. A.; ROCHA, CARLOS H. L.; ROCHA, FLAVIANE M. G.; NEVES-DA-ROCHA, JOAO; LOPES, MARCOS E. R.; SANCHES, PABLO R.; BORTOLOSSI, JULIO C.; et al. Reassessing the Use of Undecanoic Acid as a Therapeutic Strategy for Treating Fungal Infections. Mycopathologia, v. 186, n. 3, p. 327-340, JUN 2021. (15/23435-8, 19/22596-9, 18/15458-6, 18/11319-1, 09/08411-4)

CRUZ, ALINE H. S.; SANTOS, RODRIGO S. S.; MARTINS, MAIRA P.; PERES, NALU T. A.; TREVISAN, GLAUCE L. L.; MENDES, NIEGE S. S.; MARTINEZ-ROSSI, NILCE M. M.; ROSSI, ANTONIO. Relevance of Nutrient-Sensing in the Pathogenesis of Trichophyton rubrum and Trichophyton interdigitale. FRONTIERS IN FUNGAL BIOLOGY, v. 3, p. 14-pg., 2022-03-31. (19/22596-9, 18/11319-1, 09/08411-4)

LOPES, MARCOS E. R.; BITENCOURT, TAMIRES A.; SANCHES, PABLO R.; MARTINS, MAIRA P.; OLIVEIRA, VANDERCI M.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Alternative Splicing in Trichophyton rubrum Occurs in Efflux Pump Transcripts in Response to Antifungal Drugs. JOURNAL OF FUNGI, v. 8, n. 8, p. 12-pg., 2022-08-01. (18/11319-1, 15/23435-8, 19/22596-9)

MARTINS-SANTANA, LEONARDO; PETRUCELLI, MONISE FAZOLIN; SANCHES, PABLO R.; ALMEIDA, FAUSTO; MARTINEZ-ROSSI, NILCE M.; ROSSI, ANTONIO. The StuA Transcription Factor and Alternative Splicing Mechanisms Drive the Levels of MAPK Hog1 Transcripts in the Dermatophyte Trichophyton rubrum. Mycopathologia, v. 189, n. 3, p. 14-pg., 2024-06-01. (19/22596-9, 21/10255-2, 21/10359-2)