Development of co-culture of pulmonary and cerebral spheroids and cerebral organoids for the evaluation of the interaction of Cryptococcus sp. and study of the antifungal activity of peptides derived from Galleria mellonella

• Grant number: 21/14839-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2022
• End date: February 28, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Ana Marisa Fusco Almeida
• Grantee: Marcos William de Lima Gualque
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Cryptococcosis is a serious, cosmopolitan and opportunistic fungal infectious disease of public health importance that affects both immunocompromised and immunocompetent individuals. The main etiological agents are Cryptococcus neoformans and Cryptococcus gatti, which have their ecological niches in pigeon excreta and decaying matter from trees, making their dissemination constant. In order to better understand the dynamics of the interaction of this fungus, this study aims to establish a 3D culture model of brain and lung spheroids using immortalized cell lines and organoids originated from neural progenitor cells. The antifungal potential of antimicrobial peptides produced in Galleria mellonella will also be evaluated through the treatment of infections in three-dimensional models, determining the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC). For this, U-87 cells and astrocytes will be used for the formation and development of cerebral spheroids and MRC-5 and A549 cells for the development of the pulmonary spheroid. The cerebral organoid will be obtained from the ATCC cell bank (neural progenitor cell BXS117), which will be analyzed for its formation and characterized by microscopy techniques. In turn, the interaction between organoids and fungus with and without peptide treatment will be performed and the fungal load will be determined. Data will be analyzed statistically.

Scientific publications

(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)

CAMPOS, LAIS DE ALMEIDA; FIN, MARGANI TAISE; SANTOS, KELVIN SOUSA; GUALQUE, MARCOS WILLIAM DE LIMA; CABRAL, ANA KARLA LIMA FREIRE; KHALIL, NAJEH MAISSAR; FUSCO-ALMEIDA, ANA MARISA; MAINARDES, RUBIANA MARA; MENDES-GIANNINI, MARIA JOSE SOARES. Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections. PHARMACEUTICS, v. 15, n. 1, p. 32-pg., 2023-01-01. (21/14839-9)

FUSCO-ALMEIDA, ANA MARISA; SILVA, SAMANTA DE MATOS; DOS SANTOS, KELVIN SOUSA; GUALQUE, MARCOS WILLIAM DE LIMA; VASO, CAROLINA ORLANDO; CARVALHO, ANGELICA ROMAO; MEDINA-ALARCON, KAILA PETROLINA; PIRES, ANA CAROLINA MOREIRA DA SILVA; BELIZARIO, JENYFFIE ARAUJO; DE SOUZA FERNANDES, LIGIA; et al. Alternative Non-Mammalian Animal and Cellular Methods for the Study of Host-Fungal Interactions. JOURNAL OF FUNGI, v. 9, n. 9, p. 29-pg., 2023-09-01. (20/15586-4, 21/14839-9, 21/03805-6, 19/23622-3)