title: Antimicrobial activity, improved cell selectivity and mode of action of short PMAP-36-derived peptides against bacteria and Candida.
abstract: Antimicrobial peptides (AMPs) have recently attracted a great deal of attention as promising antibiotic candidates, but some obstacles such as toxicity and high synthesis cost must be addressed before developing them further. For developing short peptides with improved cell selectivity, we designed a series of modified PMAP-36 analogues. Antimicrobial assays showed that decreasing chain length in a certain range retained the high antimicrobial activity of the parental peptide and reduced hemolysis. The 18-mer peptide RI18 exhibited excellent antimicrobial activity against both bacteria and fungi, and its hemolytic activity was observably lower than PMAP-36 and melittin. The selectivity indexes of RI18 against bacteria and fungi were improved approximately 19-fold and 108-fold, respectively, compared to PMAP-36. In addition, serum did not affect the antibacterial activity of RI18 against E. coli but inhibited the antifungal efficiency against C. albicans. Flow cytometry and electron microscopy observation revealed that RI18 killed microbial cells primarily by damaging membrane integrity, leading to whole cell lysis. Taken together, these results suggest that RI18 has potential for further therapeutic research against frequently-encountered bacteria and fungi. Meanwhile, modification of AMPs is a promising strategy for developing novel antimicrobials to overcome drug-resistance.
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang, P.R. China.
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Lyu
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang, P.R. China.
authors.forename: Xiting
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Dong
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang, P.R. China.
authors.forename: Anshan
authors.initials: A
authors.lastname: Shan
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002175:Candida / Q000187:drug effects*; D002942:Circular Dichroism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C085474:PMAP-36; D011506:Proteins