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

• Grant number: 19/22596-9
• Support Opportunities: Research Projects - Thematic Grants
• Duration: May 01, 2020 - April 30, 2025
• 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: Fausto Bruno dos Reis Almeida ; Pablo Rodrigo Sanches
• Associated scholarship(s): 22/15282-0 - Alternative splicing in HSPs coding genes related to pathogenicity of dermatophyte Trichophyton rubrum, BP.IC; 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 - The functionality of the PacC transcription factor in the pH response pathway in dermatophytes, BP.DD

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

(4)

(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)

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)

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)

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)