Atividade fungicida do peptídeo antimicrobiano, Lys-A1, e sinergismo com cetoconazol contra Candida Albicans ATCC90028 e C. tropicalis ATCC750

Abstract

Candida is a pathogenic fungus associated with severe infections of difficult treatment, with a high morbidity and mortality rate. In some cases, yeasts may be in the form of cell clusters adhered to surfaces, called biofilms. Azole compounds, such as ketoconazole (KET), are used against these types of microrganisms, however, mechanisms of resistance are frequently reported in the literature. In this sense, peptides with antimicrobial activity (AMP) obtained from several living beings represent an alternative for the development of new drugs. Synthetic forms analogous to AMP Hilina a1 (Hy-a1), initially isolated from the species Hypsiboas albopunctatus, have demonstrated excellent antimicrobial efficacy, among them the Lys-a1 peptide. The objective of this work was to verify the antifungal activity of the Lys-a1 peptide on the planktonic growth and biofilm of Candida albicans ATCC90028 and Candida tropicalis ATCC750. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (CFM) were determined for Lys-a1. Then, the effect of AMP on biofilm development was determined by analyzing the biomass, metabolic rate, and morphological changes on the preformed biofilm for 72 hours for the two yeasts. Finally, the influence of Lys-a1 on the activity of ketoconazole, for determination of synergism by chekerboard was considered. The peptide has high antimicrobial activity on the microorganisms in question, 31.25 and 3.9 μg/mL for Candida albicans ATCC90028 and Candida tropicalis ATCC750, respectively. For antibiofilm activity the AMP, in concentrations of MIC, presents with partial efficiency in the elimination of the preformed biofilm. The interaction of the substances was interpreted by the Fractional Inhibitory Concentration Index (FICI) and showed a synergistic effect, establishing a 300-fold decrease in KET MIC for the two strains tested. In conclusion, these results suggest that AMP alone or in combination has a high potential for the development of new therapeutic agents for the treatment of infectious diseases caused by Candida albicans and C. tropicalis. Highlighting the possibility of using lower concentrations of azole compounds for the treatment of candidiasis.