title: Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms.
abstract: Short antimicrobial peptides with nine and eleven residues were developed against several clinically important bacterial and fungal pathogens (specifically Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Fusarium solani). Twelve analogues of previously reported peptides BP76 (KKLFKKILKFL) and Pac-525 (KWRRWVRWI) were designed, synthesized, and tested for their antimicrobial activities. Two of our eleven amino acid peptides, P11-5 (GKLFKKILKIL) and P11-6 (KKLIKKILKIL), have very low MICs of 3.1-12.5microg ml(-1) against all five pathogens. The MICs of these two peptides against S. aureus, C. albicans and F. solani are four to ten times lower than the corresponding MICs of the reference peptide BP76. P9-4 (KWRRWIRWL), our newly designed nine-amino acid analogue, also has particularly low MICs of 3.1-6.2microg ml(-1) against four of the tested pathogens; these MICs are two to eight times lower than those reported for Pac-525 (6.2-50microg ml(-1)).These new peptides (P11-5, P11-6 and P9-4) also exhibit improved stability in the presence of salts, and have low cytotoxicity as shown by the hemolysis and MTT assays. From the results of field-emission scanning electron microscopy, membrane depolarization and dye-leakage assays, we propose that these peptides exert their action by disrupting membrane lipids. Molecular dynamics simulation studies confirm that P11-6 peptide maintains relatively stable helical structure and exerts more perturbation action on the order of acyl tail of lipid bilayer.
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore, Singapore.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Qi
authors.forename: Chuncai
authors.initials: C
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Weixin
authors.initials: W
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Cao
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.forename: Wei
authors.initials: W
authors.lastname: Ning Chen
authors.forename: Chang
authors.initials: C
authors.lastname: Ming Li
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Mouad
authors.initials: M
authors.lastname: Lamrani
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
authors.forename: Susanna Su Jan
authors.initials: SS
authors.lastname: Leong
authors.forename: Matthew
authors.initials: M
authors.lastname: Wook Chang
authors.forename: Mary B
authors.initials: MB
authors.lastname: Chan-Park
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000648:ultrastructure; D002176:Candida albicans / Q000187:drug effects* / Q000648:ultrastructure; D005670:Fusarium / Q000187:drug effects* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D056004:Molecular Dynamics Simulation
chemical_list: D023181:Antimicrobial Cationic Peptides