Antibacterial and Antifungal Properties of a Novel Peptide GK-19 and
Application on Skin and Soft Tissue Infections by MRSA or Candida
Albicans
Abstract
Background and Purpose: The widespread abuse of antibiotics have led to
increasing resistance of many important human pathogens. The urgent need
to develop novel antimicrobial therapies has stimulated great interest
in antimicrobial peptides as therapeutic candidates for the treatment of
infectious diseases. Scorpion venom-derived peptide Androctonus Amoreuxi
Antimicrobial Peptide 1 (AamAP1) is a new type of host defense peptide
with broad-spectrum but moderate antimicrobial property. Most
importantly, AamAp1 has been proved to be highly hemolytic and displays
significantly high toxicity against mammalian cells. The aim of this
study was to evaluate the antimicrobial activity and mechanism of a
novel synthetic antimicrobial peptide GK-19 deriving from AamAP1 and its
derivatives. Experimental Approach: Five bacteria and three fungi were
used to evaluate the antimicrobial effect of GK-19 in vitro. Mouse
models of scalded combined with skin and soft tissue infections were
used to evaluate the antimicrobial effect of GK-19 in vivo. Key Results:
The results indicated that Gk-19 could not only inhibit Gram-positive
and Gram-negative bacterial growth but also kill fungi by permeabilizing
microbial membrane. Cellular and in vivo studies proved that GK-19
showed negligible toxicity to mammalian cells, low hemolytic activity
and high stability in plasma. Furthermore, in mouse models of scald
combined with skin and soft tissue infections induced by either
Methicillin-Resistant Staphylococcus Aureus (MRSA) or Candida Albicans,
GK-19 showed significant antimicrobial and healing effects. Conclusion
and Implications: The novel scorpion venom-derived peptide analogue
GK-19 is a promising drug candidate in the battle against
multi-resistant bacterial and fungal infections.