ANTIFUNGAL ACTION OF A SYNTHETIC PEPTIDE COMPUTATIONALLY DESIGNED

Introduction: Fungal infections are the leading cause of death in immunocompromised patients. The growing fungal resistance to existing antimicrobials associated with the difficulty in finding substances that are selective for these microorganisms has become a global health problem. Thus, it is necessary to develop new molecules capable of treating these infections and with different strategies to achieve selective toxicity. Objectives: Therefore, the objective of this work was to test a synthetic peptide, called PEPAD, designed to have specific action against pathogenic fungu. Methods and Results: Using the broth microdilution technique, the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (CFM) of the PEPAD peptide were determined against several pathogenic fungi. PEPAD showed activity against Candida albicans ATCC 5314 at 20 µM (MIC) and >20 µM (MFC), Candida tropicalis ATCC 750 at 5 µM (MIC and MFC), Candida utilis ATCC 9950 at 2.5 µM (MIC) and 5 µM (CFM) and Candida guilliermondii ATCC 6260 at 2.5 µM (MIC) and 5 µM (CFM). To evaluate the mechanism of action of PEPAD towards C. tropicalis ATCC 750, an assay was performed with the addition of exogenous ergosterol in the culture medium. The MIC of 5 µM changed to 20 µM when in contact with exogenous ergosterol, indicating that PEPAD establishes a link with ergosterol. Conclusion: The PEPAD peptide showed antifungal activity against several fungal strains at low concentrations, possibly through direct action on the cell membrane. Thus, this peptide is an attractive candidate for the development of new drugs