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Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36
Antimicrobial peptides (AMPs), which present in the non-specific immune system of organism, are amongst the most promising candidates for the development of novel antimicrobials. The modification of naturally occurring AMPs based on their residue composition and distribution is a simple and effectiv...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897731/ https://www.ncbi.nlm.nih.gov/pubmed/24466055 http://dx.doi.org/10.1371/journal.pone.0086364 |
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author | Lv, Yinfeng Wang, Jiajun Gao, He Wang, Zeyun Dong, Na Ma, Qingquan Shan, Anshan |
author_facet | Lv, Yinfeng Wang, Jiajun Gao, He Wang, Zeyun Dong, Na Ma, Qingquan Shan, Anshan |
author_sort | Lv, Yinfeng |
collection | PubMed |
description | Antimicrobial peptides (AMPs), which present in the non-specific immune system of organism, are amongst the most promising candidates for the development of novel antimicrobials. The modification of naturally occurring AMPs based on their residue composition and distribution is a simple and effective strategy for optimization of known AMPs. In this study, a series of truncated and residue-substituted derivatives of antimicrobial peptide PMAP-36 were designed and synthesized. The 24-residue truncated peptide, GI24, displayed antimicrobial activity comparable to the mother peptide PMAP-36 with MICs ranging from 1 to 4 µM, which is lower than the MICs of bee venom melittin. Although GI24 displayed high antimicrobial activity, its hemolytic activity was much lower than melittin, suggesting that GI24 have optimal cell selectivity. In addition, the crucial site of GI24 was identified through single site-mutation. An amino acid with high hydrophobicity at position 23 played an important role in guaranteeing the high antimicrobial activity of GI24. Then, lipid vesicles and whole bacteria were employed to investigate the membrane-active mechanisms. Membrane-simulating experiments showed that GI24 interacted strongly with negatively charged phospholipids and weakly with zwitterionic phospholipids, which corresponded well with the data of its biological activities. Membrane permeabilization and flow cytometry provide the evidence that GI24 killed microbial cells by permeabilizing the cell membrane and damaging membrane integrity. GI24 resulted in greater cell morphological changes and visible pores on cell membrane as determined using scanning electron microscopy (SEM) and transmission electron microscope (TEM). Taken together, the peptide GI24 may provide a promising antimicrobial agent for therapeutic applications against the frequently-encountered bacteria. |
format | Online Article Text |
id | pubmed-3897731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38977312014-01-24 Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 Lv, Yinfeng Wang, Jiajun Gao, He Wang, Zeyun Dong, Na Ma, Qingquan Shan, Anshan PLoS One Research Article Antimicrobial peptides (AMPs), which present in the non-specific immune system of organism, are amongst the most promising candidates for the development of novel antimicrobials. The modification of naturally occurring AMPs based on their residue composition and distribution is a simple and effective strategy for optimization of known AMPs. In this study, a series of truncated and residue-substituted derivatives of antimicrobial peptide PMAP-36 were designed and synthesized. The 24-residue truncated peptide, GI24, displayed antimicrobial activity comparable to the mother peptide PMAP-36 with MICs ranging from 1 to 4 µM, which is lower than the MICs of bee venom melittin. Although GI24 displayed high antimicrobial activity, its hemolytic activity was much lower than melittin, suggesting that GI24 have optimal cell selectivity. In addition, the crucial site of GI24 was identified through single site-mutation. An amino acid with high hydrophobicity at position 23 played an important role in guaranteeing the high antimicrobial activity of GI24. Then, lipid vesicles and whole bacteria were employed to investigate the membrane-active mechanisms. Membrane-simulating experiments showed that GI24 interacted strongly with negatively charged phospholipids and weakly with zwitterionic phospholipids, which corresponded well with the data of its biological activities. Membrane permeabilization and flow cytometry provide the evidence that GI24 killed microbial cells by permeabilizing the cell membrane and damaging membrane integrity. GI24 resulted in greater cell morphological changes and visible pores on cell membrane as determined using scanning electron microscopy (SEM) and transmission electron microscope (TEM). Taken together, the peptide GI24 may provide a promising antimicrobial agent for therapeutic applications against the frequently-encountered bacteria. Public Library of Science 2014-01-21 /pmc/articles/PMC3897731/ /pubmed/24466055 http://dx.doi.org/10.1371/journal.pone.0086364 Text en © 2014 Lv et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lv, Yinfeng Wang, Jiajun Gao, He Wang, Zeyun Dong, Na Ma, Qingquan Shan, Anshan Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 |
title | Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 |
title_full | Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 |
title_fullStr | Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 |
title_full_unstemmed | Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 |
title_short | Antimicrobial Properties and Membrane-Active Mechanism of a Potential α-Helical Antimicrobial Derived from Cathelicidin PMAP-36 |
title_sort | antimicrobial properties and membrane-active mechanism of a potential α-helical antimicrobial derived from cathelicidin pmap-36 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897731/ https://www.ncbi.nlm.nih.gov/pubmed/24466055 http://dx.doi.org/10.1371/journal.pone.0086364 |
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