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

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-deri...

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Bibliographic Details
Published in:Pharmaceutics 2022-09, Vol.14 (9), p.1937
Main Authors: Song, Chenghua, Wen, Ruichao, Zhou, Jiaxuan, Zeng, Xiaoyan, Kou, Zi, Zhang, Jia, Wang, Tao, Chang, Pengkang, Lv, Yi, Wu, Rongqian
Format: Article
Language:English
Subjects:
Antibiotics
Antimicrobial agents
antimicrobial peptides
Bacteria
Candida albicans
Drug resistance
Fungi
GK-19
Gram-positive bacteria
Life sciences
MRSA
Nosocomial infections
Peptides
Pulmonary arteries
Scanning electron microscopy
skin and soft tissue infections
Staphylococcus infections
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14091937