Peptides With Triplet-Tryptophan-Pivot Promoted Pathogenic Bacteria Membrane Defects

Area of Science:

• Biochemistry
• Microbiology
• Materials Science

Background:

• Antimicrobial peptides (AMPs) are crucial for innate immunity.
• Developing AMPs selective for pathogens over commensals is a therapeutic challenge.
• Targeted antimicrobial coatings offer new treatment strategies for infections.

Purpose of the Study:

• To design and evaluate novel antimicrobial peptides (AMPs) with pathogen-selective activity.
• To investigate the therapeutic potential of a specific AMP, S7, for gastrointestinal tract infections.
• To assess the safety and efficacy of S7 in preclinical models.

Main Methods:

• Construction of triplet-tryptophan-pivot peptides with varying hydrophilic amino acids.
• In vitro testing of peptide activity against pathogenic and probiotic bacteria.
• Mechanism of action studies, including drug resistance and cellular assays.
• In vivo efficacy evaluation in a mouse infection model.

Main Results:

• The peptide S7 demonstrated broad-spectrum bactericidal activity against key pathogens, including antibiotic-resistant strains.
• S7 exhibited no toxicity to the probiotic organism Lactobacillus rhamnosus.
• S7 significantly reduced bacterial load and inflammatory cytokines (TNF-α, IL-6) in vivo.
• Mechanism assays indicated low resistance probability via membrane disruption and ROS generation.

Conclusions:

• Triplet-tryptophan-pivot peptides, like S7, are effective pathogen-selective antimicrobial agents.
• S7 shows significant potential for clinical applications, including medical devices and infection therapy.
• The findings suggest broad utility for S7 in food preservation, crop protection, and human health.