Perfil antimicrobiano e citotóxico de peptídeos do néctar de Tabaco ornamental contra leveduras do gênero Candida

Abstract

Conventional antibiotics have become ineffective in the face of the growing number of infections caused by multidrug-resistant microorganisms, leading to untreatable infections. In response, innovative antimicrobial therapies are being extensively explored, emphasizing antimicrobial peptides (AMPs) in this context. These broad-spectrum molecules are capable of damaging multiple microbial components, hindering the chance of resistance development in strains. Plants are abundant sources of highly bioactive biomolecules, including AMPs, which led this study to evaluate the efficacy of six peptides from the floral nectar of ornamental tobacco against six clinically relevant yeasts (Candida albicans, Candida krusei, Candida parapsilosis e Candida tropicalis), assessing their effects on membrane integrity, intracellular reactive oxygen species accumulation, and cytotoxic potential, couplet with an investigation of peptide’s structural profile in different solvents. Among the tested peptides, only one (Pep6) exhibited activity against all tested strains in concentrations below 100μM. Further assays demonstrated its fungicidal properties and its ability to target yeasts through membrane permeabilization/disruption and oxidative damage induction, without causing any harm at the tested concentrations to human erythrocytes, murine fibroblasts, or Danio rerio embryos. Moreover, structural data predicted its ability to adopt an α-helical pattern in membrane- mimetic environments. Subsequent studies, using clinically validated methodologies, reported an almost fourfold reduction in MIC values for Pep6 (Nicotianin-I) against C. tropicalis. Additionally, synergistic effects with caspofungin and fluconazole were also confirmed. Finally, the peptide’s ability to interact with membranes and penetrate cells were also experimentally confirmed. These findings highlight the potential of Nicotianin-I and may support future studies aimed at optimizing its efficacy as an antimicrobial agent