SELECTION OF THERAPEUTIC TARGETS AND/OR BIOMARKERS FROM GLOBAL RESPONSE TRANSCRIPTIONAL OF ALVEOLAR MACROPHAGES INFECTED BY H. capsulatum BIOFILMS

• Grant number: 16/11836-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2016
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Ana Marisa Fusco Almeida
• Grantee: Ana Marisa Fusco Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Cleslei Fernando Zanelli ; Francisco Javier Enguita ; Maria José Soares Mendes Giannini ; Maria Lucia Taylor da Cunha e Mello

Abstract

Histoplasma capsulatum variety capsulatum is a fungal pathogen which causes histoplasmosis that occurs as a result of inhalation of microconidea from mycelial phase, primarily affecting the lung which occurs the yeast differentiation, inducing a pulmonary infection and dissemination to other organs. Recently, a correlation between the H. capsulatum infection mode, and the formation of biofilms was established. Additionally our group evaluated for the first time the miRNA expression profile in human macrophages infected with yeasts of the fungus on biofilm and planktonic form, and the results showed a differential response of the host cell compared to uninfected cells and compared to the biofilm mode. In this context, the formation of H. capsulatum biofilms has been associated with nosocomial infections and for this reason, is emerging the identification of differential biomarkers and target that may be selected in order to establish a new therapeutic approach for histoplasmosis. Based on this, this work aims to analyze the differential transcriptome between alveolar macrophages (Mø) infected with H. capsulatum yeast structured in biofilms and planktonic cultures, such that uninfected cells will be used as control. The complete sequencing of the transcribed regions will be performed using an Illumina platform to identify potential candidate genes that encoding key proteins and characterize the transcriptional signature of infection by H. caspulatum in its different forms of growth identifying biomarkers that show the existence of biofilms in the interaction H. capsulatum-host cells. (AU)

Scientific publications

(6)

(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)

VASO, CAROLINA ORLANDO; BILA, NIURA MADALENA; PANDOLFI, FABIANA; DE VITA, DANIELA; BORTOLAMI, MARTINA; CARVALHO BONATTI, JEAN LUCAS; DE MORAES SILVA, ROSANGELA APARECIDA; CARVALHO GONCALVES, LARISSA NAIARA; TUDINO, VALERIA; COSTI, ROBERTA; et al. Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures. PHARMACEUTICS, v. 14, n. 5, p. 23-pg., 2022-05-01. (20/15586-4, 19/22188-8, 18/02785-9, 17/18388-6, 16/11836-0)

COSTA-ORLANDI, CAROLINE B.; SARDI, JANAINA C. O.; PITANGUI, NAYLA S.; DE OLIVEIRA, HAROLDO C.; SCORZONI, LILIANA; GALEANE, MARIANA C.; MEDINA-ALARCON, KAILA P.; MELO, WANESSA C. M. A.; MARCELINO, MONICA Y.; BRAZ, JAQUELINE D.; et al. Fungal Biofilms and Polymicrobial Diseases. JOURNAL OF FUNGI, v. 3, n. 2, JUN 2017. (15/03700-9, 15/14023-8, 13/10917-9, 16/11836-0)

VASO, CAROLINA ORLANDO; PANDOLFI, FABIANA; BILA, NIURA MADALENA; DE VITA, DANIELA; BORTOLAMI, MARTINA; SOARES MENDES-GIANNINI, MARIA JOSE; TUDINO, VALERIA; COSTI, ROBERTA; COSTA-ORLANDI, CAROLINE BARCELOS; FUSCO-ALMEIDA, ANA MARISA; et al. Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives. PHARMACEUTICS, v. 14, n. 3, p. 19-pg., 2022-03-01. (20/15586-4, 16/11836-0, 19/22188-8, 17/18388-6)

FREGONEZI, NATHALIA FERREIRA; OLIVEIRA, LARIANE TEODORO; SINGULANI, JUNYA DE LACORTE; MARCOS, CAROLINE MARIA; DOS SANTOS, CLAUDIA TAVARES; TAYLOR, MARIA LUCIA; MENDES-GIANNINI, MARIA JOSE SOARES; DE OLIVEIRA, HAROLDO CESAR; FUSCO-ALMEIDA, ANA MARISA. Heat Shock Protein 60, Insights to Its Importance in Histoplasma capsulatum: From Biofilm Formation to Host-Interaction. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, JAN 22 2021. (18/15877-9, 15/14023-8, 16/11836-0, 17/06658-9, 16/17048-4)

GALEANE, MARIANA C.; GOMES, PAULO C.; SINGULANI, JUNYA DE L.; DE SOUZA, BIBIANA M.; PALMA, MARIO S.; MENDES-GIANNINI, MARIA J. S.; ALMEIDA, ANA M. F.. Study of mastoparan analog peptides against Candida albicans and safety in zebrafish embryos (Danio rerio). FUTURE MICROBIOLOGY, v. 14, n. 13, p. 1087-1097, SEP 2019. (17/06658-9, 16/11836-0)

MARCELINO, MONICA YONASHIRO; BORGES, FELIPE AZEVEDO; SCORZONI, LILIANA; SINGULANI, JUNYA DE LACORTE; GARMS, BRUNA CAMBRAIA; NIEMEYER, JULIA CARINA; GUERRA, NAYRIM BRIZUELA; PEGORIN BRASIL, GIOVANA SANT'ANA; MUSSAGY, CASSAMO USSEMANE; DE OLIVEIRA CARVALHO, FRANCISCO ADRIANO; et al. Synthesis and characterization of gold nanoparticles and their toxicity in alternative methods to the use of mammals. JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING, v. 9, n. 6, DEC 2021. (17/19603-8, 16/11836-0)