High Specific Selectivity and Membrane-Active Mechanism of Synthetic Cationic Hybrid Antimicrobial Peptides Based on the Peptide FV7.
Hybrid peptides integrating different functional domains of peptides have many advantages, such as remarkable antimicrobial activity, lower hemolysis and ideal cell selectivity, compared with natural antimicrobial peptides. FV7 (FRIRVRV-NH₂), a consensus amphiphilic sequence was identified as being analogous to host defense peptides. In this study, we designed a series of hybrid peptides FV7-LL-37 (17-29) (FV-LL), FV7-magainin 2 (9-21) (FV-MA) and FV7-cecropin A (1-8) (FV-CE) by combining the FV7 sequence with the small functional sequences LL-37 (17-29) (LL), magainin 2 (9-21) (MA) and cecropin A (1-8) (CE) which all come from well-described natural peptides. The results demonstrated that the synthetic hybrid peptides, in particular FV-LL, had potent antibacterial activities over a wide range of Gram-negative and Gram-positive bacteria with lower hemolytic activity than other peptides. Furthermore, fluorescent spectroscopy indicated that the hybrid peptide FV-LL exhibited marked membrane destruction by inducing outer and inner bacterial membrane permeabilization, while scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that FV-LL damaged membrane integrity by disrupting the bacterial membrane. Inhibiting biofilm formation assays also showed that FV-LL had similar anti-biofilm activity compared with the functional peptide sequence FV7. Synthetic cationic hybrid peptides based on FV7 could provide new models for combining different functional domains and demonstrate effective avenues to screen for novel antimicrobial agents.
Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China. 15684244286@163.com.
Tingting
T
Tan
Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China. woodyneau@163.com.
Di
D
Wu
Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China. laowu2003@wfu.edu.cn.
Weizhong
W
Li
College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China. zhengxinjilin@126.com.
Xin
X
Zheng
Institute of Animal Nutrition and Feed Science, College of Animal Science, Zhejiang University, Hangzhou 310058, China. wfli@zju.edu.cn.
Weifen
W
Li
Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China. asshan@neau.edu.cn.
Anshan
A
Shan
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004355:Drug Stability; D006461:Hemolysis; D008826:Microbial Sensitivity Tests; D010539:Permeability / Q000187:drug effects; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides
FV7; amino acid; antimicrobial peptide; biofilm; microbiology