Anti-Candida and antibiofilm activity of epinecidin-1 and its variants

Abstract

To boost the stability and antimicrobial efficacy of the antimicrobial peptide (AMP) epinecidin-1, we previously engineered two variants -- variant-1 and variant-2--by substituting alanine and histidine residues with lysine. This modification led to improved structural integrity and antibacterial function. Our current study builds on this foundation by assessing the anti-Candida capabilities of epinecidin-1 and its variants against test organisms Candida albicans, Candida tropicalis, and Candida krusei. Both variants exhibited potent anti-Candida activity, particularly in disrupting biofilm formation. Minimum Inhibitory Concentrations (MICs) were found to be decreased for both variants compared to the original epinecidin-1 peptide, with variant-2 exhibiting the strongest activity. Electron microscopy confirmed that the mechanism of action involves pore formation and the induction of reactive oxygen species in the Candida cell membrane. Computational analysis showed the peptides have a high tendency to interact with the Candida cell membrane proteins like Exo-B-(1,3)-Glucanase, Secreted aspartic proteinase (Sap) 1, and N-terminal domain adhesin: Als 9-2, to prevent biofilm development.