Enhanced Antimicrobial Activity of N-Terminal Derivatives of a Novel Brevinin-1 Peptide from The Skin Secretion of <i>Odorrana schmackeri</i>
Xiaowei Zhou,
Yue Liu,
Yitian Gao,
Yuanxing Wang,
Qiang Xia,
Ruimin Zhong,
Chengbang Ma,
Mei Zhou,
Xinping Xi,
Chris Shaw,
Tianbao Chen,
Di Wu,
Hang Fai Kwok,
Lei Wang
Affiliations
Xiaowei Zhou
Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University; Shaoguan 512005, China
Yue Liu
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Yitian Gao
College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
Yuanxing Wang
State Key Lab of Food Science and Technology, Nanchang University, Nanchang 330047, China
Qiang Xia
Department of Food Science and Engineering, Key Laboratory of Animal Protein Food Processing Technology of Zhejiang Province, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315832, China
Ruimin Zhong
Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University; Shaoguan 512005, China
Chengbang Ma
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Mei Zhou
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Xinping Xi
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Chris Shaw
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Tianbao Chen
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Di Wu
Chemical Biology Research Centre, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China
Hang Fai Kwok
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR
Lei Wang
Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Antimicrobial peptides (AMPs) are promising therapeutic alternatives compared to conventional antibiotics for the treatment of drug-resistant bacterial infections. However, the application of the overwhelming majority of AMPs is limited because of the high toxicity and high manufacturing costs. Amphibian skin secretion has been proven to be a promising source for the discovery and development of novel AMPs. Herein, we discovered a novel AMP from the skin secretion of Odorrana schmackeri, and designed the analogues by altering the key factors, including conformation, net charge and amphipathicity, to generate short AMPs with enhanced therapeutic efficacy. All the peptides were chemically synthesised, followed by evaluating their biological activity, stability and cytotoxicity. OSd, OSe and OSf exhibited broad-spectrum antibacterial effects, especially OSf, which presented the highest therapeutic index for the tested bacteria. Moreover, these peptides displayed good stability. The results from scanning electron microscopy and transmission electron microscopy studies, indicated that brevinin-OS, OSd, OSe and OSf possessed rapid bactericidal ability by disturbing membrane permeability and causing the release of cytoplasmic contents. In addition, OSd, OSe and OSf dramatically decreased the mortality of waxworms acutely infected with MRSA. Taken together, these data suggested that a balance between positive charge, degrees of α-helicity and hydrophobicity, is necessary for maintaining antimicrobial activity, and these data successfully contributed to the design of short AMPs with significant bactericidal activity and cell selectivity.
