Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells

PeerJ

article

Haohao Zhu¹  Xiyan Ding¹  Wei Li¹  Tulin Lu¹  Chengbang Ma²  Xinping Xi²  Lei Wang²  Mei Zhou²  Roberta Burden²  Tianbao Chen² 

[1] School of Pharmacy, Nanjing University of Chinese Medicine;School of Pharmacy, The Queen’s University Belfast

关键词: Molecular cloning;    Skin secretion;    Dermaseptin;    Antimicrobial peptide;    Cell viability.;   

DOI  :  10.7717/peerj.5635

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Two novel peptides belonging to the dermaseptin family, namely DRS-CA-1 and DRS-DU-1, were encoded from cDNA libraries derived from the skin secretions of Phyllomedusa camba and Callimedusa (Phyllomedusa) duellmani. Both natural peptides are highly-conserved and exhibited high potency against wild-type Gram-positive, Gram-negative bacteria, yeast and antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa) (MICs 4–8 µM) with no obvious hemolytic activity. Collectively these results suggest that both peptides may have potential as novel antibiotics. Additionally, DRS-DU-1 exhibited selective cytotoxicity to tumor cells. The truncated analogue, DP-1 and TAT-fused DP-1 (namely DP-2) were subsequently synthesised. It showed that DP-1 had low antimicrobial activity, no hemolytic and cytotoxicity to tumor cells. However, DP-2 possessed strong antimicrobial activity and the similar selective, no obvious hemolytic activity and cytotoxicity on normal human cells, but enhanced cytotoxicity to tumor cells of DRS-DU-1. These findings indicate that the N-terminus of the dermaseptins may contribute to their bioactivity, and that addition of the TAT peptide can improve biological activity. The results provide a new insight for designing novel peptide-based antimicrobial or anticancer agents with low hemolytic activity and cytotoxicity.

【 授权许可】

CC BY