Effect of Sequence and Structural Properties on 14-Helical ?-Peptide Activity against Candida albicans Planktonic Cells and Biofilms
Abstract
?-Peptides (? -amino acid oligomers) that mimic the amphiphilic, helical, and cationic properties of natural antimicrobial peptides have previously been shown to display antifungal activity against planktonic Candida albicans cells. ?-Peptides offer several advantages over conventional peptides composed of ?-amino acid residues, including conformational stability, resistance to proteases, and activity at physiological salt concentrations. We examined sequence–activity relationships toward both planktonic C. albicans cells and C. albicans bio-films, and the results suggest a toxicity mechanism involving membrane disruption. A strategy for fluorescently labeling a ?-peptide without diminishing antifungal activity was devised; labeled ?-peptides penetrated the cell membrane and accumulated in the cytoplasm of both planktonic and biofilm-associated cells.
The labeled -peptide was detected only in metabolically inactive cells, which suggests that ?-peptide entry is correlated with cell death. The presence of a ?-peptide at a concentration near the minimum inhibitory concentration completely prevented planktonic C. albicans cells from forming a biofilm, suggesting that ?-peptides may be useful in preventing fungal colonization and biofilm formation.
References
Amy J. Karlsson, William C. Pomerantz, Keane J. Neilsen, Samuel H. Gellman, Sean P. Palecek (2009). “Effect of sequence and structural properties on 14-Helical ?-peptides activity against Candida Albicans planktonic cells and biofilms”. ACS Chemical Biology 7:567-579.