Congresso Brasileiro de Microbiologia 2023

Congresso Brasileiro de Microbiologia 2023

Resumo: 917-1

917-1

Selenium compound shows antifungal effect on Cryptococcus gattii and inhibits its virulence factors.

Autores:

Letícia Serafim da Costa (ICB - USP - Instituto de Ciências Biomédicas da Universidade de São Paul) ; Isadora Maria de Oliveira (CNPEM - Centro Nacional de Pesquisa em Energia e Materiais) ; Daniel Felipe Freitas de Jesus (ICB - USP - Instituto de Ciências Biomédicas da Universidade de São Paul) ; Kelly Ishida (ICB - USP - Instituto de Ciências Biomédicas da Universidade de São Paul) ; Hélio Alexandre Stefani (FCF - USP - Faculdade de Ciências Farmacêuticas USP)

Resumo:

Cryptococcus spp. are fungal pathogens cited on the World Health Organization List of Fungal Priority Pathogens due to limited antifungal therapy to treat the cryptococcosis and high rates of mortality. Cryptococcus gattii species is responsible for causing the disease in immunocompetent hosts because the virulence factors expression such as polysaccharide capsule, titan cells, melanin and biofilm production in addition to its ability to escape of the host's immune system response. In this regard, the search for new molecules with potential antifungal against C. gattii is necessary. The aim of this study is to evaluate the action of compound LQA_78 on C. gattii growth and its virulence factors. The broth microdilution technique was performed to determine the minimum inhibitory concentration (MIC) of amphotericin B (AMB), fluconazole (FLC), flucytosine (5-FC), and LQA_78 against a standard strain (R265) and clinical isolates (n=5), using planktonic cells and dispersed cells from biofilms. The metabolic activity of sessile cells from biofilms was determined by the XTT reduction method after treatment of mature biofilms with LQA_78 for 48 hours. The yeasts with enlarged capsule (NcC) and titan cell (Tc) were induced in vitro using specific media and both cells were treated with LQA_78 to determine the MIC values. After treatments, capsule morphometry and determination of capsular permeability using fluorophore rhodamine isothiocyanate-dextran was performed. For melanization assay the yeasts were cultivated on minimum medium containing L-DOPA without or with LQA_78 and laccase activity was measured. C. gattii strains were susceptible to AMB (0.03-1 μg/ml) and 5-FC (0.5-4 μg/ml) but showed reduced susceptibility to FLC (2-64 μg/ml). LQA_78 showed inhibitory effect on C. gattiiC. gattii cells and on the main virulence factors associated with C. gattii pathogenesis. These results also lead to new paths of research to be followed such as molecular mechanisms and in vivo models.

Palavras-chave:

cryptococcus, morphotype, capsule, antifungal, selenium

Agência de fomento:

Fundação de Amparo à Pesquisa do Estado de São Paulo (2021/01279-5), Conselho Nacional de Desenvolvimento Científico e Tecnológico (405556/2018-7), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (finance code 001).