Avaliação da atividade antimicrobiana de tensoativos derivados de aminoácidos frente a isolados de candida spp. resistentes ao fluconazol e de S. Aureus resistentes a meticilina

Abstract

In recent years, an increase in the incidence of blood infections caused by caused by Candida spp. as well as Staphylococcus aureus, being related to high morbidity and mortality among hospitalized patients. Therefore, it is necessary to search for new treatments, and, in this context, due to toxicological and environmental concerns, the amino acid-based surfactants have attracted special attention for its biodegradable characteristics and its antimicrobial potential. This study was evaluated the antimicrobial activity of two chemically synthesized products, derived based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM), by the Consejo Superior de Investigaciones Científicas (CSIC) against Candida spp. resistant to fluconazole strains and methicillin- resistant Staphylococcus aureus (MRSA) strains, in the planktonic form and in the formed biofilms, as well as their probable mechanisms of action, using flow cytometry techniques and molecular docking to evaluate their interaction with enzymes of S. aureus. The compounds were also evaluated under ADMET parameters, considering absorption, distribution, metabolism, excretion, toxicity in order to explore their potential for the development of new drugs. The evaluation of the antimicrobial effect was carried out with the tested products, using the broth microdilution test. The interaction with amphotericin B against Candida spp. resistant to fluconazole strains was analyzed through the Fractional Inhibitory Concentration Calculation (FICI). The strains used presented MIC for LPAM and LTAM products that ranged from 8.12-16.24 μg/mL for Candida spp and MRSA. When combined with amphotericin B, a synergistic effect was observed in all strains of Candida spp. Regarding anti biofilm activity, the products showed activity against Candida spp biofilm and show no activity against MRSA biofilm. Cytometry analysis indicated that LPAM and LTAM products cause a reduction in the cell viability of Candida spp. and MRSA, cause alteration of the membrane potential of Candida spp., production of reactive oxygen species and externalization of phosphatidylserine in Candida spp. and reduced DNA damage in Candida spp. and significant in MRSA. In silico assays revealed the existence of molecular bonds such as hydrogen bonds and through ADMET assays it was concluded that LPAM and LTAM compounds are promising pharmacological active principles against microbial agents.