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Comparative mode of action of the antimicrobial peptide melimine and its derivative Mel4 against Pseudomonas aeruginosa.

ABSTRACT: Melimine and Mel4 are chimeric cationic peptides with broad-spectrum antimicrobial activity. They have been shown to be highly biocompatible in animal models and human clinical trials. The current study examined the mechanism of action of these two antimicrobial peptides against P. aeruginosa. The effect of the peptides of endotoxin neutralization, and their interactions with cytoplasmic membranes using DiSC(3)-5 and Sytox green, Syto-9 and PI dyes were analysed. Release of ATP and DNA/RNA were determined using ATP luminescence and increase in OD_260?nm. The bacteriolytic ability of the peptides was determined by measuring decreases in OD_620?nm. Both the peptides neutralized LPS suggesting their interaction with lipid A. Cytoplasmic membrane was disrupted within 30?seconds, which correlated with reductions in cellular viability. At 2?minutes melimine or Mel4, released 75% and 36% cellular ATP respectively (P?

SUBMITTER: Yasir M

PROVIDER: S-EPMC6506473 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Comparative mode of action of the antimicrobial peptide melimine and its derivative Mel4 against Pseudomonas aeruginosa.

Yasir Muhammad M Dutta Debarun D Willcox Mark D P MDP

Scientific reports 20190508 1

Melimine and Mel4 are chimeric cationic peptides with broad-spectrum antimicrobial activity. They have been shown to be highly biocompatible in animal models and human clinical trials. The current study examined the mechanism of action of these two antimicrobial peptides against P. aeruginosa. The effect of the peptides of endotoxin neutralization, and their interactions with cytoplasmic membranes using DiSC(3)-5 and Sytox green, Syto-9 and PI dyes were analysed. Release of ATP and DNA/RNA were ...[more]

PMID: 31068610

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Project description:Bacterial colonization and biofilm development on medical devices can lead to infection. Antimicrobial peptide-coated surfaces may prevent such infections. Melimine and Mel4 are chimeric cationic peptides showing broad-spectrum antimicrobial activity once attached to biomaterials and are highly biocompatible in animal models and have been tested in Phase I and II/III human clinical trials. These peptides were covalently attached to glass using an azidobenzoic acid linker. Peptide attachment was confirmed using X-ray photoelectron spectroscopy and amino acid analysis. Mel4 when bound to glass was able to adopt a more ordered structure in the presence of bacterial membrane mimetic lipids. The ability of surface bound peptides to neutralize endotoxin was measured along with their interactions with the bacterial cytoplasmic membrane which were analyzed using DiSC(3)-5 and Sytox green, Syto-9, and PI dyes with fluorescence microscopy. Leakage of ATP and nucleic acids from cells were determined by analyzing the surrounding fluid. Attachment of the peptides resulted in increases in the percentage of nitrogen by 3.0% and 2.4%, and amino acid concentrations to 0.237 nmole and 0.298 nmole per coverslip on melimine and Mel4 coated surfaces, respectively. The immobilized peptides bound lipopolysaccharide and disrupted the cytoplasmic membrane potential of Pseudomonas aeruginosa within 15 min. Membrane depolarization was associated with a reduction in bacterial viability by 82% and 63% for coatings melimine and Mel4, respectively (p < 0.001). Disruption of membrane potential was followed by leakage of ATP from melimine (1.5 ± 0.4 nM) or Mel4 (1.3 ± 0.2 nM) coated surfaces compared to uncoated glass after 2 h (p < 0.001). Sytox green influx started after 3 h incubation with either peptide. Melimine coatings yielded 59% and Mel4 gave 36% PI stained cells after 4 h. Release of the larger molecules (DNA/RNA) commenced after 4 h for melimine (1.8 ± 0.9 times more than control; p = 0.008) and after 6 h with Mel4 (2.1 ± 0.2 times more than control; p < 0.001). The mechanism of action of surface bound melimine and Mel4 was similar to that of the peptides in solution, however, their immobilization resulted in much slower (approximately 30 times) kinetics.

Dataset Information

Comparative mode of action of the antimicrobial peptide melimine and its derivative Mel4 against Pseudomonas aeruginosa.

Publications

Comparative mode of action of the antimicrobial peptide melimine and its derivative Mel4 against Pseudomonas aeruginosa.

Similar Datasets

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