Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells
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-t...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2018-09-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/5635.pdf |
| _version_ | 1827612079364767744 |
|---|---|
| author | Haohao Zhu Xiyan Ding Wei Li Tulin Lu Chengbang Ma Xinping Xi Lei Wang Mei Zhou Roberta Burden Tianbao Chen |
| author_facet | Haohao Zhu Xiyan Ding Wei Li Tulin Lu Chengbang Ma Xinping Xi Lei Wang Mei Zhou Roberta Burden Tianbao Chen |
| author_sort | Haohao Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T08:17:16Z |
| format | Article |
| id | doaj.art-0cc6f8fee11541f39968d703eee6efe3 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:17:16Z |
| publishDate | 2018-09-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-0cc6f8fee11541f39968d703eee6efe32023-12-02T22:00:53ZengPeerJ Inc.PeerJ2167-83592018-09-016e563510.7717/peerj.5635Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cellsHaohao Zhu0Xiyan Ding1Wei Li2Tulin Lu3Chengbang Ma4Xinping Xi5Lei Wang6Mei Zhou7Roberta Burden8Tianbao Chen9School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, The Queen’s University Belfast, Belfast, United KingdomSchool of Pharmacy, The Queen’s University Belfast, Belfast, United KingdomSchool of Pharmacy, The Queen’s University Belfast, Belfast, United KingdomSchool of Pharmacy, The Queen’s University Belfast, Belfast, United KingdomSchool of Pharmacy, The Queen’s University Belfast, Belfast, United KingdomSchool of Pharmacy, The Queen’s University Belfast, Belfast, United KingdomTwo 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.https://peerj.com/articles/5635.pdfMolecular cloningSkin secretionDermaseptinAntimicrobial peptideCell viability. |
| spellingShingle | Haohao Zhu Xiyan Ding Wei Li Tulin Lu Chengbang Ma Xinping Xi Lei Wang Mei Zhou Roberta Burden Tianbao Chen 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 Molecular cloning Skin secretion Dermaseptin Antimicrobial peptide Cell viability. |
| title | Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells |
| title_full | Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells |
| title_fullStr | Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells |
| title_full_unstemmed | Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells |
| title_short | Discovery of two skin-derived dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells |
| title_sort | discovery of two skin derived dermaseptins and design of a tat fusion analogue with broad spectrum antimicrobial activity and low cytotoxicity on healthy cells |
| topic | Molecular cloning Skin secretion Dermaseptin Antimicrobial peptide Cell viability. |
| url | https://peerj.com/articles/5635.pdf |
| work_keys_str_mv | AT haohaozhu discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT xiyanding discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT weili discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT tulinlu discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT chengbangma discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT xinpingxi discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT leiwang discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT meizhou discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT robertaburden discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells AT tianbaochen discoveryoftwoskinderiveddermaseptinsanddesignofatatfusionanaloguewithbroadspectrumantimicrobialactivityandlowcytotoxicityonhealthycells |