Taheri, B and Mohammadi, M and Momenzadeh, N and Farshadzadeh, Z and Roozbehani, M and Dehghani, P and Hajian, S and Darvishi, S and Shamseddin, J (2019) Substitution of lysine for isoleucine at the center of the nonpolar face of the antimicrobial peptide, piscidin-1, leads to an increase in the rapidity of bactericidal activity and a reduction in toxicity. Infection and Drug Resistance, 12. pp. 1629-1647. ISSN 11786973
Full text not available from this repository.Abstract
Purpose: Piscidin-1 is an effective antimicrobial peptide (AMP) against a variety of microbes. However, its toxicity has been reported as a limitation for its potential therapeutic applications. The toxicity of piscidin-1 may be related to the long nonpolar face of this AMP. Here, we investigated different piscidin-1 analogs to reach a peptide with the reduced toxicity. Material and methods: In vitro and in vivo antibacterial activity and toxicity of piscidin-1 analogs generated by replacement of isoleucine at the border (I9) or the center (I16) of the nonpolar face of piscidin-1 by alanine or lysine were investigated. Results: The results indicated that among all peptides, piscidin-1 with the highest HPLC retention time (RT) and I16K-piscidin-1 with the lowest RT had the highest and lowest cytotoxicity, respectively. Although I16K-piscidin-1 possessed the same MIC value as the parent peptide (piscidin-1) and other analogs, I16K-piscidin-1 exhibited a higher rapidity of bactericidal action at 5×MIC. The β-galactosidase leakage and propidium iodide staining assays indicated a higher pore-forming capacity of I16K-piscidin-1 relative to the parent peptide (piscidin-1). Taken together, RT is suggested to have a direct association with the toxicity and an inverse association with the rapidity of bactericidal action and pore-forming capacity. After infection of mice with clinical colistin-resistant Acinetobacter baumannii or clinical methicillin-resistant Staphylococcus aureus strains, treatment with I16K-piscidin-1, but not piscidin-1 and other analogs, resulted in a significantly stronger bactericidal potency. Furthermore, I16K-piscidin-1 exhibited the lowest in vivo toxicity. Conclusion: Overall, in vitro and in vivo comparison of piscidin-1 and its analogs together documented that replacement of isoleucine at the center of the nonpolar face of piscidin-1 (I16) by lysine leads to not only a decrease in toxicity potential but also an increase in bactericidal potential.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Acinetobacter baumannii،Antimicrobial peptide،Piscidin-1،Staphylococcus aureus،Toxicity activity |
| Subjects: | QW Microbiology and Immunology |
| Divisions: | Research Center > Persian Gulf Marine Biotechnology Research Center |
| Depositing User: | خدیجه شبانکاره |
| Date Deposited: | 03 Jan 2021 10:10 |
| Last Modified: | 03 Jan 2021 10:10 |
| URI: | http://eprints.bpums.ac.ir/id/eprint/9252 |
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