Abstract
BackgroundAntimicrobial peptides (AMPs) are a class of antimicrobial agents with broad-spectrum activities. Several reports indicate that cationic AMPs bind to the negatively charged bacterial membrane causing membrane depolarization and damage. However, membrane depolarization and damage may be insufficient to elicit cell death, thereby suggesting that other mechanism(s) of action could be involved in this phenomenon. In this study, we investigated the antimicrobial activity of a novel antimicrobial peptide, TP359, against two strains of Pseudomonas aeruginosa, as well as its possible mechanisms of action.ResultsTP359 proved to be bactericidal against P. aeruginosa as confirmed by the reduced bacteria counts, membrane damage and cytoplasmic membrane depolarization. In addition, it was non-toxic to mouse J774 macrophages and human lung A549 epithelial cells. Electron microscopy analysis showed TP359 bactericidal effects by structural changes of the bacteria from viable rod-shaped cells to those with cell membrane damages, proceeding into the efflux of cytoplasmic contents and emergence of ghost cells. Gene expression analysis on the effects of TP359 on outer membrane biogenesis genes underscored marked down-regulation, particularly of oprF, which encodes a major structural and outer membrane porin (OprF) in both strains studied, indicating that the peptide may cause deregulation of outer membrane genes and reduced structural stability which could lead to cell death.ConclusionOur data shows that TP359 has potent antimicrobial activity against P aeruginosa. The correlation between membrane damage, depolarization and reduced expression of outer membrane biogenesis genes, particularly oprF may suggest the bactericidal mechanism of action of the TP359 peptide.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0808-2) contains supplementary material, which is available to authorized users.
Highlights
Antimicrobial peptides (AMPs) are a class of antimicrobial agents with broad-spectrum activities
Our results revealed the following: (i) both strains of P. aeruginosa were sensitive to TP359, (ii) TP359 showed no toxic effects against human lung epithelial A549 and mouse J774 macrophage cell lines, (iii) TP359 caused membrane damage, as shown by scanning electron microscopy (SEM), transmission electron microscopy (TEM), LIVE/DEAD stain and membrane depolarization assay and (iv) TP359 down-regulated P. aeruginosa membrane biogenesis and peptidoglycan synthesis associated genes
The lack of toxicity of AMPs to eukaryotic cells may be due to their membrane composition, which consists of zwitterionic phospholipids that are neutral in net charge [6]
Summary
Antimicrobial peptides (AMPs) are a class of antimicrobial agents with broad-spectrum activities. We investigated the antimicrobial activity of a novel antimicrobial peptide, TP359, against two strains of Pseudomonas aeruginosa, as well as its possible mechanisms of action. There is an increasing need for antimicrobial agents with novel mechanisms of action, which target essential cellular metabolic processes and pathways. Cationic AMPs are small positively charged amphipathic peptides; having both hydrophilic and hydrophobic ends, which enable the molecules to be soluble in aqueous medium and to penetrate lipid-rich membranes of bacterial cells. The negative charge is due to composition of the membranes of bacteria, which is different from eukaryotic cells This difference partially explains the sensitivity of bacterial cells to AMPs and the lack of toxicity to eukaryotic cells [6]
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