Effect of sequence and structural properties on 14-helical beta-peptide activity against Candida albicans planktonic cells and biofilms.
Beta-peptides (beta-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. Beta-peptides offer several advantages over conventional peptides composed of alpha-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 biofilms, and the results suggest a toxicity mechanism involving membrane disruption. A strategy for fluorescently labeling a beta-peptide without diminishing antifungal activity was devised; labeled beta-peptides penetrated the cell membrane and accumulated in the cytoplasm of both planktonic and biofilm-associated cells. The labeled beta-peptide was detected only in metabolically inactive cells, which suggests that beta-peptide entry is correlated with cell death. The presence of a beta-peptide at a concentration near the minimum inhibitory concentration completely prevented planktonic C. albicans cells from forming a biofilm, suggesting that beta-peptides may be useful in preventing fungal colonization and biofilm formation.
Karlsson
Amy J
AJ
Department of Chemical & Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Pomerantz
William C
WC
Neilsen
Keane J
KJ
Gellman
Samuel H
SH
Palecek
Sean P
SP
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D010455:Peptides