PSN-PC: A Novel Antimicrobial and Anti-Biofilm Peptide from the Skin Secretion of Phyllomedusa-camba with Cytotoxicity on Human Lung Cancer Cell.

Xianhui Wu,Chengbang Ma,Yue Wu,Lei Wang,Jinhuo Pan,Mei Zhou,Tianbao Chen,Xinping Xi

doi:10.3390/molecules22111896

Abstract

Peptides derived from amphibian skin secretion are promising drug prototypes for combating widespread infection. In this study, a novel peptide belonging to the phylloseptin family of antimicrobial peptides was isolated from the skin secretion of the Phyllomedusa camba, namely phylloseptin-PC (PSN-PC). The biosynthetic precursor was obtained by molecular cloning and the mature peptide sequence was confirmed through tandem mass spectrometry (MS/MS) fragmentation sequencing in the skin secretion. The synthetic replicate exhibited a broad spectrum antimicrobial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans at concentrations of 2, 2, 8, 32 and 2 µM, respectively. It also showed the capability of eliminating S. aureus biofilm with a minimal biofilm eradication concentration of 8 µM. The haemolysis of this peptide was not significant at low concentrations but had a considerable increase at high concentrations. Additionally, this peptide showed an anti-proliferation effect on the non-small cell lung cancer cell line (NCI-H157), with low cytotoxicity on the human microvascular endothelial cell line (HMEC-1). The discovery of the novel peptide may provide useful clues for new drug discoveries.

Highlights

Amphibian skin secretion consists of various bioactive peptides that play an essential role in amphibian survival
Some antimicrobial peptides (AMPs) have been reported to be capable of inhibiting biofilm formation as well as eradicating mature biofilm [5], which makes bacteria 1,000-fold more resistant to conventional antimicrobial agents than their planktonic counterparts
Further investigation of the cell-membrane permeabilisation of S. aureus after the 2 h incubation with corresponding concentrations of PSN-PC and bacteria cells were performed and the results showed that PSN-PC induced about 45% of cell-membrane permeabilisation at 2 μM on S. aureus (Figure 6b)

Summary

Introduction

Amphibian skin secretion consists of various bioactive peptides that play an essential role in amphibian survival. These peptides demonstrated multifunctional activities against Gram-negative and Gram-positive bacteria, fungi, enveloped viruses and even cancer cells [1]. Some other peptides are considered potentially to be immunomodulatory and anti-diabetic agents [2], and even contraceptives, as they can be cytotoxic to sperm [3]. These skin-derived antimicrobial peptides (AMPs) are especially predominant and demonstrate board spectrum antimicrobial activity, which make them potential drug candidates in the treatment of bacterial infections. Some AMPs have been reported to be capable of inhibiting biofilm formation as well as eradicating mature biofilm [5], which makes bacteria 1,000-fold more resistant to conventional antimicrobial agents than their planktonic counterparts

Methods

Results

Conclusion