Computational approach, scanning electron and fluorescence microscopies revealed insights into the action mechanisms of anticandidal peptide Mo-CBP3-PepIII.

Abstract Aims The Candida genus is composed of opportunistic pathogens that threaten public health. Given the increase in resistance to current drugs, it is necessary to develop new drugs to treat infections by these pathogens. Antimicrobial peptides are promising alternative molecules with low cost, broad action spectrum and low resistance induction. This study aimed to clarify the action mechanisms of synthetic peptides against Candida albicans. Main methods The mode of action of the anticandidal peptides Mo-CBP3-PepIII were analyzed through molecular dynamics and quantum biochemistry methods against Exo-β-1,3-glucanase (EXG), vital to cell wall metabolism. Furthermore, scanning electron (SEM) and fluorescence (FM) microscopies were employed to corroborate the in silico data. Key findings Mo-CBP3-PepIII strongly interacted with EXG (−122.2 kcal mol−1) at the active site, higher than the commercial inhibitor pepstatin. Also, molecular dynamics revealed the insertion of Mo-CBP3-PepIII into the yeast membrane. SEM analyses revealed that Mo-CBP3-PepIII induced cracks and scars of the cell wall and FM analyses confirmed the pore formation on the Candida membrane. Significance Mo-CBP3-PepIII has strong potential as a new drug with a broad spectrum of action, given its different mode of action compared to conventional drugs.