Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lv, Yinfeng, Wang, Jiajun, Gao, He, Wang, Zeyun, Dong, Na, Ma, Qingquan, Shan, Anshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782300292451139584
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
work_keys_str_mv AT lvyinfeng antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36
AT wangjiajun antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36
AT gaohe antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36
AT wangzeyun antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36
AT dongna antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36
AT maqingquan antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36
AT shananshan antimicrobialpropertiesandmembraneactivemechanismofapotentialahelicalantimicrobialderivedfromcathelicidinpmap36