Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors

• Grant number: 15/23435-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2016
• End date: October 09, 2019
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Nilce Maria Martinez-Rossi
• Grantee: Tamires Aparecida Bitencourt
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/03847-7 - Molecular characterization of mechanisms involved in pathogenicity and cell signaling in fungi, AP.TEM

Abstract

Fungi respond to extracellular stimuli by activating signal transduction pathways responsible for physiological mechanisms that allow adaptation to stress, the development of cell defense, and tolerance. The antifungal drugs induce cellular stress responses needed to overcome their toxic effects, possibly allowing the survival of the fungus. Knowledge of the molecular mechanism of the adaptive responses of fungi to adverse conditions is important for understanding the biology of these microorganisms, which may reveal essential metabolic pathways that allow their survival and consequently new cellular targets for the development of effective drugs to control these infections. Transcriptome studies during T. rubrum exposure to compounds with antifungal activity have led to identify genes involved in the adaptive response to stress, and the elucidation of mechanisms of action of drugs such as terbinafine, acriflavine, amphotericin B, fluconazole, among others. However, with the development of new molecular techniques such as RNA-Seq it was demonstrated that virtually any eukaryotic genome is transcribed and that these transcripts may undergo various processes such as alternative splicing and riboswitches, in response to environmental stimuli. Therefore, this project aims to identify possible RNA processing that can contribute to modulate the susceptibility to antifungal drugs in T. rubrum, and compare these results with those from other dermatophytes. (AU)

Scientific publications

(19)

(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)

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)

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)

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)

BITENCOURT, TAMIRES APARECIDA; MACEDO, CLAUDIA; FRANCO, MATHEUS ELOY; ROCHA, MARINA CAMPOS; MORELI, IGOR SAWASAKI; MICHELOTO CANTELLI, BRUNA ALINE; SANCHES, PABLO RODRIGO; BELEBONI, RENE OLIVEIRA; MALAVAZI, IRAN; PASSOS, GERALDO ALEIXO; et al. Trans-chalcone activity against Trichophyton rubrum relies on an interplay between signaling pathways related to cell wall integrity and fatty acid metabolism. BMC Genomics, v. 20, MAY 22 2019. (16/22701-9, 12/02920-7, 15/23435-8)

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)

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)

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)

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)

DE ABREU, MARIANA HEINZEN; BITENCOURT, TAMIRES APARECIDA; FRANCO, MATHEUS ELOY; MORELI, IGOR SAWASAKI; MICHELOTTO CANTELLI, BRUNA ALINE; KOMOTO, TATIANA TAKAHASI; MARINS, MOZART; FACHIN, ANA LUCIA. Expression of genes containing tandem repeat patterns involved in the fungal-host interaction and in the response to antifungals in Trichophyton rubrum. MYCOSES, v. 63, n. 6, APR 2020. (15/23435-8, 16/22701-9, 19/10514-8)

MICHELOTTO CANTELLI, BRUNA ALINE; BITENCOURT, TAMIRES APARECIDA; KOMOTO, TATIANA TAKAHASI; BELEBONI, RENE OLIVEIRA; MARINS, MOZART; FACHIN, ANA LUCIA. Caffeic acid and licochalcone A interfere with the glyoxylate cycle of Trichophyton rubrum. BIOMEDICINE & PHARMACOTHERAPY, v. 96, p. 1389-1394, DEC 2017. (16/22701-9, 15/23435-8, 14/23841-3)

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)

KOMOTO, TATIANA TAKAHASI; BERNARDES, TAYNA MINERVINA; MESQUITA, THAIS BALTHAZAR; BUSO BORTOLOTTO, LUIS FELIPE; SILVA, GABRIEL; BITENCOURT, TAMIRES APARECIDA; BAEK, SEUNG JOON; MARINS, MOZART; FACHIN, ANA LUCIA. Chalcones Repressed the AURKA and MDR Proteins Involved in Metastasis and Multiple Drug Resistance in Breast Cancer Cell Lines. Molecules, v. 23, n. 8, AUG 2018. (16/22701-9, 15/23435-8, 12/15862-5)

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)

LOPES, LUCIA; BITENCOURT, TAMIRES A.; LANG, ELZA A. S.; SANCHES, PABLO R.; PERES, NALU T. A.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Genes coding for LysM domains in the dermatophyte Trichophyton rubrum: A transcription analysis. Medical Mycology, v. 58, n. 3, p. 372-379, APR 2020. (15/23435-8)

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)

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)

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)