Repository of Research and Investigative Information

Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

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

(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.

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Official URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC65854...

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 5xMIC. The beta-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
Keywords: antimicrobial peptide; piscidin-1; toxicity activity; Staphylococcus aureus; Acinetobacter baumannii IN-VITRO; LYSOZYME
Subjects: QW Microbiology and Immunology > QW 1-300 Microbiology
Divisions: Research Vice-Chancellor Department > Infectious and Tropical Diseases Research Center
Depositing User: هدی فهیم پور
URI: http://eprints.hums.ac.ir/id/eprint/6589

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