title: Truncated antimicrobial peptides from marine organisms retain anticancer activity and antibacterial activity against multidrug-resistant Staphylococcus aureus.
abstract: Antimicrobial peptides (AMPs) were recently determined to be potential candidates for treating drug-resistant bacterial infections. The aim of this study was to develop shorter AMP fragments that combine maximal bactericidal effect with minimal synthesis cost. We first synthesized a series of truncated forms of AMPs (anti-lipopolysaccharide factor from shrimp, epinecidin from grouper, and pardaxin from Pardachirus marmoratus). The minimum inhibitory concentrations (MICs) of modified AMPs against ten bacterial species were determined. We also examined the synergy between peptide and non-peptide antibiotics. In addition, we measured the inhibitory rate of cancer cells treated with AMPs by MTS assay. We found that two modified antibacterial peptides (epinecidin-8 and pardaxin-6) had a broad range of action against both gram-positive and gram-negative bacteria. Furthermore, epinecidin and pardaxin were demonstrated to have high antibacterial and anticancer activities, and both AMPs resulted in a significant synergistic improvement in the potencies of streptomycin and kanamycin against methicillin-resistant Staphylococcus aureus. Neither AMP induced significant hemolysis at their MICs. In addition, both AMPs inhibited human epithelial carcinoma (HeLa) and fibrosarcoma (HT-1080) cell growth. The functions of these truncated AMPs were similar to those of their full-length equivalents. In conclusion, we have successfully identified shorter, inexpensive fragments with maximal bactericidal activity. This study also provides an excellent basis for the investigation of potential synergies between peptide and non-peptide antibiotics, for a broad range of antimicrobial and anticancer activities.
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, 1 Roosevelt Road, Section 4, Taipei 10617, Taiwan.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Lin
authors.forename: Cho-Fat
authors.initials: CF
authors.lastname: Hui
authors.forename: Jyh-Yih
authors.initials: JY
authors.lastname: Chen
authors.forename: Jen-Leih
authors.initials: JL
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D029941:Fish Proteins / Q000737:chemistry / Q000494:pharmacology*; D005397:Fish Venoms / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006461:Hemolysis; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D060829:Arthropod Proteins; D029941:Fish Proteins; D005397:Fish Venoms; D010446:Peptide Fragments; C521392:epinecidin-1, Epinephelus coioides; C017603:pardaxin