Biochemical Property and In Vivo Efficacies of Novel Val/Arg-rich Antimicrobial Peptide

Abstract

A novel α-helical antimicrobial peptide G6 rich in Val/Arg residues has been screened previously. In this study, we further evaluated the biochemical stability, interaction with whole bacteria, and in vivo therapeutic or prophylactic role of the peptide in Salmonella typhimurium-infected mice. The results showed that G6 exhibited strong resistance to pH, heat, and salts. But G6 lost the antimicrobial activity when treated with proteolytic enzymes. G6 had no toxicity on mammalian cell. An intraperitoneal model of sepsis caused by Salmonella typhimurium was established in mice. G6 was administered intraperitoneally 1 h before or after mice were infected with Salmonella typhimurium. For the mice given peptide post-bacterial infection, the mortality of the mice and the peritoneal bacterial counts were significantly lower in the groups that were administered 2.5 mg/kg BW and 5.0 mg/kg BW of G6 (P < 0.05) compared to the PBS-treated group. Similar trend was obtained when G6 was given 1 h prior to Salmonella typhimurium infection. Peptide-membrane experiments showed that G6 was effective in permeabilizing the outer and inner membrane in a dose dependent manner, indicating that the peptide targets the cell membrane. Taken together, the results revealed that the peptide G6 may provide a useful alternative to antibiotic agents to treat or prevent bacterial infections.

Prokaryotic expression and antimicrobial mechanism of XPF-St7-derived α-helical peptides

“…Therefore, increasing the number of positive charges in an antimicrobial peptide may enhance its antibiotic activity. Arg residue is important for the initial electrostatic attraction of AMPs to the surface of cell membrane . In this study, XPF4 and XPF6 showed remarkable antibacterial activity and only mild hemolytic activity, suggesting that positive charges are critical for the antibiotic activity and selectivity of antimicrobial peptides, which is consistent with the previous studies .…”

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era

“…According to the helical‐wheel projection, Ma et al designed a small combinatorial library of Val/Arg‐rich peptides, and peptide G6 was found to have optimal cell selectivity. G6 has been further demonstrated to reduce peritoneal bacterial counts and increase survival after Salmonella typhimurium infection . Further studies were conducted to assess the effect of net charge and Pro on the activity of Val/Arg‐rich peptides.…”

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

“…The BODIPY-TR-cadaverine (BC) displacement assay was performed to analyze the LPS binding ability as previously studied ( Ma et al, 2012 ). At the beginning, the LPS-probe solution was formed by 4h incubation of 50μg/ml LPS (derived from Pseudomonas aeruginosa , purchased from Sigma-Aldrich, Shanghai, China) and 5μg/mlBC dye in Tris buffer.…”