Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans

Abstract

The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.

Recent developments in membrane targeting antifungal agents to mitigate antifungal resistance

“…5h). 136 Studies demonstrated that the developed peptide exhibited minimal toxicity against RBCs (Fig. 5i).…”

Antimicrobial Peptides: Avant-Garde Antifungal Agents to Fight against Medically Important Candida Species

“…After day 10, it was observed that GK-19 significantly reduced the wound area (more than 95%) compared to the other treatments, and the histological examination revealed the full recovery of GK-19-treated mice, as their skin showed a large number of neovascularization and new-born hair follicle tissues. GK-19 also had a favorable toxicity/safety profile in vitro and in vivo [ 58 ].…”

Combined Therapy of Probiotic Microcapsules and Bomidin in Vibrio parahaemolyticus–Infected Rats

“…In the context of alternatives to traditional antibiotics, antimicrobial peptides (AMPs) have become promising products due to their unique advantages. AMPs achieve their antibacterial effect by improving membrane permeability, inhibiting metabolism, and adjusting immune responses [17]. Furthermore, AMPs do not easily create drug resistance.…”