A Novel Antimicrobial Peptide (Kassinatuerin-3) Isolated from the Skin Secretion of the African Frog, Kassina senegalensis.

Hui Wang,Tianbao Chen,Qiang Du,Xiaoling Chen,Haoyang He,Chengbang Ma,Chris Shaw,Mei Zhou,Xinping Xi,Lei Wang,Minjie Wei

doi:10.3390/biology9070148

Abstract

Amphibian skin secretions are remarkable sources of novel bioactive peptides. Among these, antimicrobial peptides have demonstrated an outstanding efficacy in killing microorganisms via a general membranolytic mechanism, which may offer the prospect of solving specific target-driven antibiotic resistance. Here, the discovery of a novel defensive peptide is described from the skin secretion of the African frog, Kassina senegalensis. Named kassinatuerin-3, it was identified through a combination of “shot-gun” cloning and MS/MS fragmentation sequencing. Subsequently, a synthetic replicate was subjected to biofunctional evaluation. The results indicated that kassinatuerin-3 possessed antimicrobial activity against Gram-positive bacteria but no effect against Gram-negative bacteria. Additionally, it was active in biofilm eradication on S. aureus and MRSA and in the antiproliferation of selected cancer cell lines. Moreover, it had a very mild hemolytic effect, which demonstrated a high therapeutic index for kassinatuerin-3. Collectively, although kassinatuerin-3 did not demonstrate remarkable bioactivities compared with other natural or synthetic antimicrobial peptides (AMPs), it offered a new insight into the design of antimicrobial derivatives.

Highlights

In the past several decades, the increasing problem of antimicrobial resistance to conventional antibiotics has made the discovery and development of novel antimicrobial agents increasingly important [1,2]
The alignments of the amino acid sequences of the peptide precursors identified from K. senegalensis and K. maculata demonstrated the high degree of primary structural conservation among the signal peptide and spacer domains (Figure 2)
We report the identification and biological evaluation of a novel antimicrobial peptide, kassinatuerin-3, from the skin secretion of the African frog, K. senegalensis

Summary

Introduction

In the past several decades, the increasing problem of antimicrobial resistance to conventional antibiotics has made the discovery and development of novel antimicrobial agents increasingly important [1,2]. Antimicrobial peptides (AMPs) from different sources are well-recognized as a potential solution to resistance problems due to their different mechanism of action against highly conserved membrane structures [6,7] and their antibiofilm effects [8] Among these sources, such as single-celled microorganisms, insects and other invertebrates, plants, amphibians, birds, fish, and mammals, Biology 2020, 9, 148; doi:10.3390/biology9070148 www.mdpi.com/journal/biology. Thousands of AMPs have been discovered in amphibian skin secretions, and these peptides exhibit a high degree of amino acid sequence diversity and peptide chain lengths ranging from 10 to 50 residues [10] Based on their structural characteristics, amphibian skin-derived AMPs have been classified into different superfamilies, such as the brevinin and temporin superfamilies from Ranidae frogs [11]; dermaseptin, phylloxin and phylloseptin from Hylidae frogs [12]; bombinin and bombinin H from Bombinatoridae toads [13]; and magainin from the Pipidae species [14]. An analogue of magainin from Xenopus skin, has been evaluated in two phase III clinical trials for bacterial infections of diabetic foot ulcers [17,18,19]

Methods

Results

Discussion

Conclusion