Study of the response to antifungal and fungal-host interaction of T.rubrum dermatophyte using different models of infection

• Grant number: 16/22701-9
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2017
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Ana Lucia Fachin Saltoratto
• Grantee: Ana Lucia Fachin Saltoratto
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 18/17951-1 - "Study of the response to antifungal and fungal-host interaction of Trichophyton rubrum dermatophyte using different models of infection", BP.TT; 18/11300-9 - Study of the response to antifungal and fungal-host interaction of Trichophyton rubrum dermatophyte using different models of infection, BP.TT

Abstract

Trichophyton rubrum is the most frequent causative agent of superficial dermatomycoses in Brazil and worldwide. Dermatophytes are keratinolytic fungi, which have the ability to utilize various host proteins (mainly keratin) as a source of nutrients in the skin, nails and hair. In addition, these infections also affect immunocompromised patients, being able to behave in an invasive way causing serious infections. Despite the clinical importance of infections caused by T. rubrum, the molecular processes of the fungus-host relationship were not fully understood. The T.rubrum dermatophyte is able to modulate the innate immune response of the host cell causing the non-recognition of the pathogen by the cellular defense system, reducing the human immune response, facilitating the infectious process. MicroRNAs are small non-coding regulatory RNAs that have been identified as an important part of the immune response to a variety of pathogens, modulating primarily the intensity of the inflammatory response, and may be a potent therapeutic target. In order to better understand the complex fungus-host relationship, it is necessary to use appropriate models of in vitro infection, among which the use of keratinocytes of the stratum corneum of the skin, macrophages, the use of fragments of nails, explants of skin derived from plastic surgery, in addition to models that consist of the addition of proteins such as elastin and keratin in culture medium. Additionally, knowledge about fungal virulence factors involved in host infection can be used as targets for the development of new antifungal agents. Currently, there are few drugs on the market and their targets are limited because of the shared similarities between fungal and mammalian cells. The demand for new antifungals of natural origin with new specific targets is increasing, due to an increase in the frequency of infectious diseases, as well as the emergence of strains resistants to the current treatment. The objective of this project is to analyze the cellular and molecular events of the antifungal response and the fungus-host interaction in the T. rubrum dermatophyte using different infection models (culture medium added with protein substrates, human keratinocyte cell line and human macrophages cell line). The results can be contribute to the discovery of new molecular targets that can be explored by antifungal agents, in order to develop more effective and specific compounds for the treatment of dermatophytoses. (AU)

Scientific publications

(8)

(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)

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)

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)

CANTELLI, BRUNA ALINE; SEGURA, GABRIELA GONZALEZ; BITENCOURT, TAMIRES APARECIDA; DE ABREU, MARIANA HEINZEN; PETRUCELLI, MONISE FAZOLIN; PERONNI, KAMILA; SANCHES, PABLO RODRIGO; BELEBONI, RENE OLIVEIRA; DA SILVA JUNIOR, WILSON ARAUJO; MARTINEZ-ROSSI, NILCE MARIA; et al. Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia. JOURNAL OF FUNGI, v. 9, n. 5, p. 14-pg., 2023-05-12. (19/10514-8, 16/22701-9)

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)

PETRUCELLI, MONISE FAZOLIN; PERONNI, KAMILA; SANCHES, PABLO RODRIGO; KOMOTO, TATIANA TAKAHASI; MATSUDA, JOSIE BUDAG; DA SILVA JR, WILSON ARAUJO; BELEBONI, RENE OLIVEIRA; MARTINEZ-ROSSI, NILCE MARIA; MARINS, MOZART; FACHIN, ANA LUCIA. Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction. GENES, v. 9, n. 7, JUL 2018. (16/22701-9)

PETRUCELLI, MONISE FAZOLIN; MATSUDA, JOSIE BUDAG; PERONI, KAMILA; SANCHES, PABLO RODRIGO; SILVA, JR., WILSON ARAUJO; BELEBONI, RENE OLIVEIRA; MARTINEZ-ROSSI, NILCE MARIA; MARINS, MOZART; FACHIN, ANA LUCIA. The Transcriptional Profile of Trichophyton rubrum Co-Cultured with Human Keratinocytes Shows New Insights about Gene Modulation by Terbinafine. PATHOGENS, v. 8, n. 4, DEC 2019. (16/22701-9)

SEGURA, GABRIELA GONZALEZ; CANTELLI, BRUNA ALINE; PERONNI, KAMILA; SANCHES, PABLO RODRIGO; KOMOTO, TATIANA TAKAHASI; RIZZI, ELEN; BELEBONI, RENE OLIVEIRA; DA SILVA JUNIOR, WILSON ARAUJO; MARTINEZ-ROSSI, NILCE MARIA; MARINS, MOZART; et al. Cellular and Molecular Response of Macrophages THP-1 during Co-Culture with Inactive Trichophyton rubrum Conidia. JOURNAL OF FUNGI, v. 6, n. 4, DEC 2020. (19/10514-8, 16/22701-9)

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)