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Open AccessArticle

Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities

1
Department of Bioscience and Biotechnology, Research Institute for Bioactive-Metabolome Network, Konkuk University, Seoul 05029, Korea
2
Chuncheon Center, Korea Basic Science Institute, Chuncheon 24341, Korea
3
Protein Structure Group, Korea Basic Science Institute, Ochang, Cheongju, Chung-Buk 28199, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(19), 4895; https://doi.org/10.3390/ijms20194895
Received: 4 September 2019 / Revised: 29 September 2019 / Accepted: 30 September 2019 / Published: 2 October 2019
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis. View Full-Text
Keywords: pseudin-2; antimicrobial peptide; antisepsis, peptide antibiotics pseudin-2; antimicrobial peptide; antisepsis, peptide antibiotics
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MDPI and ACS Style

Jang, M.; Kim, J.; Choi, Y.; Bang, J.; Kim, Y. Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities. Int. J. Mol. Sci. 2019, 20, 4895.

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