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Design and characterization of a new hybrid peptide from LL-37 and BMAP-27

Background and purpose: The world is heading to a post-antibiotic era where the treatment of bacterial infections will not be possible even with well-known last-line antibiotics. Unfortunately, the emergence of multidrug resistant bacterial strains is uncontrollable, and the humanity will face a lif...

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Autores principales: Al Tall, Yara, Abualhaijaa, Ahmad, Alsaggar, Mohammad, Almaaytah, Ammar, Masadeh, Majed, Alzoubi, Karem H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503343/
https://www.ncbi.nlm.nih.gov/pubmed/31118709
http://dx.doi.org/10.2147/IDR.S199473
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author Al Tall, Yara
Abualhaijaa, Ahmad
Alsaggar, Mohammad
Almaaytah, Ammar
Masadeh, Majed
Alzoubi, Karem H
author_facet Al Tall, Yara
Abualhaijaa, Ahmad
Alsaggar, Mohammad
Almaaytah, Ammar
Masadeh, Majed
Alzoubi, Karem H
author_sort Al Tall, Yara
collection PubMed
description Background and purpose: The world is heading to a post-antibiotic era where the treatment of bacterial infections will not be possible even with well-known last-line antibiotics. Unfortunately, the emergence of multidrug resistant bacterial strains is uncontrollable, and the humanity will face a life-threatening fate unless new antimicrobial agents with new bacterial target sites are promptly developed. Herein, we design a hybrid antimicrobial peptide (B1) from helical parts taken from the parent peptides: LL-37 and BMAP-27. The purpose of this design is to improve the potency and enhance the toxicity profile of the parent peptides. Methods: Rational design was used to hybridize two antimicrobial peptides, in which two helical parts from the bovine analog BMAP-27, and the human cathelicidin LL-37 were used to generate a novel peptide (B1). The physicochemical properties were checked using in silico methods. The antimicrobial activities were tested against nine control and resistant strains of Gram-positive and Gram-negative bacteria. On the other hand, the antibiofilm activities were tested against four resistant strains. The cytotoxicity on mammalian cells was tested using HEK293, and the hemolysis activity was also investigated on human blood. Finally, synergistic studies were performed with four conventional antibiotics against four resistant strains of Gram-positive and Gram-negative bacteria. Results: The new peptide B1 exhibited broad-spectrum activities against all tested strains. The concentration against planktonic cells ranged between 10 and 20 µM. However, 40–60 µM were needed to eradicate the biofilms. B1 showed reduced toxicity toward mammalian cells with minimal hemolysis risk. On the other hand, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their minimum inhibitory concentration values. The concentrations of B1 peptide combined with the tested antibiotics were also decreased markedly down to 0.5 µM in some cases. Conclusion: B1 is a hybrid peptide from two cathelicidin peptides. It showed an improved activity compared to parent peptides. The hybridization was successful in this study. It generated a new potent broad-spectrum antimicrobial. The toxicity profile was improved, and the synergism with the convention antibiotics showed promising results.
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spelling pubmed-65033432019-05-22 Design and characterization of a new hybrid peptide from LL-37 and BMAP-27 Al Tall, Yara Abualhaijaa, Ahmad Alsaggar, Mohammad Almaaytah, Ammar Masadeh, Majed Alzoubi, Karem H Infect Drug Resist Original Research Background and purpose: The world is heading to a post-antibiotic era where the treatment of bacterial infections will not be possible even with well-known last-line antibiotics. Unfortunately, the emergence of multidrug resistant bacterial strains is uncontrollable, and the humanity will face a life-threatening fate unless new antimicrobial agents with new bacterial target sites are promptly developed. Herein, we design a hybrid antimicrobial peptide (B1) from helical parts taken from the parent peptides: LL-37 and BMAP-27. The purpose of this design is to improve the potency and enhance the toxicity profile of the parent peptides. Methods: Rational design was used to hybridize two antimicrobial peptides, in which two helical parts from the bovine analog BMAP-27, and the human cathelicidin LL-37 were used to generate a novel peptide (B1). The physicochemical properties were checked using in silico methods. The antimicrobial activities were tested against nine control and resistant strains of Gram-positive and Gram-negative bacteria. On the other hand, the antibiofilm activities were tested against four resistant strains. The cytotoxicity on mammalian cells was tested using HEK293, and the hemolysis activity was also investigated on human blood. Finally, synergistic studies were performed with four conventional antibiotics against four resistant strains of Gram-positive and Gram-negative bacteria. Results: The new peptide B1 exhibited broad-spectrum activities against all tested strains. The concentration against planktonic cells ranged between 10 and 20 µM. However, 40–60 µM were needed to eradicate the biofilms. B1 showed reduced toxicity toward mammalian cells with minimal hemolysis risk. On the other hand, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their minimum inhibitory concentration values. The concentrations of B1 peptide combined with the tested antibiotics were also decreased markedly down to 0.5 µM in some cases. Conclusion: B1 is a hybrid peptide from two cathelicidin peptides. It showed an improved activity compared to parent peptides. The hybridization was successful in this study. It generated a new potent broad-spectrum antimicrobial. The toxicity profile was improved, and the synergism with the convention antibiotics showed promising results. Dove 2019-04-30 /pmc/articles/PMC6503343/ /pubmed/31118709 http://dx.doi.org/10.2147/IDR.S199473 Text en © 2019 Al Tall et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Al Tall, Yara
Abualhaijaa, Ahmad
Alsaggar, Mohammad
Almaaytah, Ammar
Masadeh, Majed
Alzoubi, Karem H
Design and characterization of a new hybrid peptide from LL-37 and BMAP-27
title Design and characterization of a new hybrid peptide from LL-37 and BMAP-27
title_full Design and characterization of a new hybrid peptide from LL-37 and BMAP-27
title_fullStr Design and characterization of a new hybrid peptide from LL-37 and BMAP-27
title_full_unstemmed Design and characterization of a new hybrid peptide from LL-37 and BMAP-27
title_short Design and characterization of a new hybrid peptide from LL-37 and BMAP-27
title_sort design and characterization of a new hybrid peptide from ll-37 and bmap-27
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503343/
https://www.ncbi.nlm.nih.gov/pubmed/31118709
http://dx.doi.org/10.2147/IDR.S199473
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