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

• Published in: Life sciences (1973) Vol. 281; p. 119775
• Main Authors: Amaral, Jackson L., Souza, Pedro F.N., Oliveira, Jose T.A., Freire, Valder N., Sousa, Daniele O.B.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 15.09.2021; Elsevier BV
• Subjects: Antiinfectives and antibacterials; Antimicrobial peptides; Candida; Cell walls; Computer applications; Drug resistance; Drugs; Fluorescence; Health risks; Low resistance; Membrane insertion; Membranes; Metabolism; Mo-CBP3-PepIII; Mode of action; Molecular dynamics; Opportunist infection; Pathogens; Peptides; Pore formation; Public health; Quantum biochemistry; Scars; Synthetic peptides; Yeasts; Molecular dynamics; Mo-CBP3-PepIII; Quantum biochemistry; Membrane insertion
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119775

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. 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. 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. 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. •Mo-CBP3-PepIII interacts with Exo-β-1,3-glucanase stronger than conventional inhibitor.•Dynamics simulation revealed how Mo-CBP3-PepIII penetrates in the yeast membrane.•SEM analysis revealed cell wall damage in C. albicans induced by Mo-CBP3-PepIII.•Fluorescence microscopy analysis revealed pore formation in the C. albicans membrane.•Mo-CBP3-PepIII induces ROS overproduction C. albicans cells.