Design and Mode of Action of a New Synthetic Antibacterial Peptide against Pseudomonas aeruginosa

Authors
Armineh Azadian 1
Hamideh Mahmoodzadeh Hosseini 2
Seyed Ali Mirhosseini 2
Soghra Khani 3
Jafar Amani 2
1 1Department of Biology ،Faculty of Basic Sciences, Islamic Azad University, Science and Research Branch, Tehran, Iran
2 Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
3 Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
10.66224/ibj.5380
Abstract
Background: Research into antimicrobial peptides (AMPs) and other novel antimicrobial strategies continues to be a focus of the scientific community to address the growing challenges posed by antibiotic resistance. The aim of this study was the specific bioinformatic design of a novel hybrid AMP that combines the potent antibacterial properties of Temporins and Brevinin while minimizing its cytotoxic effects.

Methods: The N-terminal of Brevinin peptides and the C-terminal of Temporin peptide were selected. To optimize the peptide, we replaced the amino acids at positions 1, 3, and 7 with glycine, lysine, and lysine, respectively. Various approaches were used to assess physicochemical characteristics, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), cytotoxicity, apoptosis, hemolytic activity, and reactive oxygen species generation.

Results: The novel peptide had 57% hydrophobicity and four positive electric charges due to its lysine amino acid composition. The synthesized peptide exhibited MIC and MBC values of 80 µM against Pseudomonas aeruginosa. According to the MTT assay, the peptide showed neither cytotoxic nor hemolytic effects on human cells. The results of electron microscopy showed that this peptide can disrupt the integrity of P. aeruginosa membrane cells and induce morphological changes in their surface structure.

Conclusion: This research suggests that the synthetic peptide could serve as a promising potential therapeutic agent to combat antibiotic-resistant strains of P. aeruginosa.
Keywords
Antibacterial peptides
Pseudomonas aeruginosa
Temporins
Brevinins
Iranian Biomedical Journal
Volume 30, Issue 1 - Serial Number 122
January and February 2026
Pages 81-89