Avaliação da atividade antifúngica, sinérgica e antibiofilme do etomidato frente a cepas de Candida spp. resistentes ao fluconazol

• Ano de defesa: 2020
• Autor(a) principal: Sá, Lívia Gurgel do Amaral Valente
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Candida; Etomidato; Resistência Microbiana a Medicamentos; Biofilmes; Fluconazol
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/53647

Candidiasis is related to high hospital expenses, patients with candidiasis generate more costs for the health system and stay on average more days in hospital. Candida spp. is between the fourth and sixth most isolated pathogen from bloodstream infections. The redirection of drugs appears as a therapeutic alternative to deal with drug resistance. The present study aimed to evaluate the antifungal activity of anesthetic etomidate (ETO) isolated and associated with azoles against resistant strains of Candida spp. in planktonic form and biofilm, in addition to investigating the production of manoproteins and the interaction with ALS3 through molecular documentation. In addition, also investigate the possible mechanisms of action using flow cytometry techniques. Therefore, 11 clinical strains of Candida spp. were subjected to acid microdilution tests using etomidate alone and associated with fluconazole (FLC) and itraconazole (ITR). The evaluation of the interaction of drugs was performed through the Calculation of Fractional Inhibitory Concentration (FICI). It was also selected or potentially isolated from biofilms in formation, and its activity isolated and associated from biofilms formed. In order to investigate possible mechanisms of action, 1 Candida albicans head was subjected to membrane integrity tests, assessment of transmembrane mitochondrial potential (Δψm), detection of reactive oxygen species, annexing by annexin V and assessment of DNA damage. The strains of Candida spp. presented MIC for etomidate ranging from 125 to 250 μg / mL. Regarding the combination of drugs, etomidate and itraconazole showed synergism for all strains tested. However, the combination of etomidate and fluconazole was shown to be synergistic for only 4 strains. No antagonism was observed in any of the combinations. Etomidate and its associations showed activity against the biofilm formed, reducing up to 50% of cell viability, showing a synergistic effect also against biofilms. Regarding the biofilm in formation, etomidate also showed activity and was able to decrease the production of manoproteins on the surface of C. albicans cells. In the molecular docking tests, it was possible to observe that the etomidate was in the same region as the hepta-threonine, being close to the Ser170 residue (catalytic triad) and the amino acid residue that has an adhesion role (Lys59). Cytometry tests showed that etomidate alone and combined with the tested azoles caused a decrease in cell viability, alteration of the membrane potential and production of reactive oxygen species, no DNA damage was found.