Title: A cleavable chimeric peptide-R7: enhancing the dual-function of LPS neutralization and antibacterial properties against MDR E. coli

Biography:

Xiumin Wang has been focusing on this special narrow field of AMP for many years, especially design of different antibacterial agents, antibacterial activity, and mode of actions.

Abstract

Gram-negative bacteria are the most common cause of sepsis and lipopolysaccharide (LPS) is a major inducer of sepsis. LBP14, a core domain (residues 86-99) of LPS-binding protein, has strong ability to neutralize LPS. Lfcin7 (L7) is a bovine lactoferricin (LfcinB) derivative, which possesses potent antibacterial activity. In this study, the cleavable chimeric peptide-R7 was generated by connecting LBP14 and L7 via a cleavable linker to improve antibacterial and anti-inflammatory activities. Compared to parent peptide L7, the antibacterial activity of R7 against Escherichia coli, Salmonella typhimurium and Staphylococcus aureus was increased by 2~4-fold; the ability of R7 to neutralize LPS was markedly higher than that of L7. R7 had low hemolysis to mouse red blood cells but some toxicity towards RAW264.7 cells. R7 could be cleaved by furin in vitro in a time-dependent manner, and could release L7 and LBP14 in serum. In vivo, after prevention with R7, the survival rate of the mice challenged with multidrug-resistant (MDR) E. coli or LPS was 100%, higher than that of L7 (60% and 40%). R7 significantly inhibited inflammatory response by down-regulating tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels and by up-regulating interleukin-10 (IL-10) and intestinal alkaline phosphatase (IAP) levels. It suggests that R7 may be promising dual-function candidates as novel antibacterial and anti-endotoxin agents to prevent bacterial sepsis.