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Antimicrobial properties and membrane-active mechanism of a potential α-helical antimicrobial derived from cathelicidin PMAP-36.
- Source :
-
PloS one [PLoS One] 2014 Jan 21; Vol. 9 (1), pp. e86364. Date of Electronic Publication: 2014 Jan 21 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- Cell Membrane metabolism
Hemolysis drug effects
Hydrophobic and Hydrophilic Interactions
Melitten pharmacology
Peptides pharmacology
Phospholipids metabolism
Protein Structure, Secondary
Cathelicidins
Anti-Infective Agents chemistry
Anti-Infective Agents pharmacology
Antimicrobial Cationic Peptides chemistry
Bacteria drug effects
Cell Membrane drug effects
Peptides chemistry
Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24466055
- Full Text :
- https://doi.org/10.1371/journal.pone.0086364