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

Abstract

Development of probiotic-ineffective antimicrobial peptides (AMPs)-based coatings that can kill pathogenic bacteria at low concentrations but are essentially harmless (even high concentrations) to probiotic organisms is a relatively new trend for therapy against GI tract infections. In this study, a series of triplet-tryptophan-pivot peptides with various hydrophilic amino acids was constructed. One AMP in particular, S7, showed bactericidal activity against <i>Staphylococcus epidermidis</i>, <i>Pseudomonas aeruginosa</i>, <i>Escherichia coli</i> and antibiotic-resistant <i>Staphylococcus aureus</i>, yet was shown to be harmless to <i>Lactobacillus rhamnosus</i>, a key GI tract commensal. Furthermore, antibacterial mechanism assays, drug resistance assays, and mouse model tests suggested that S7 was useful in a clinical setting as it proved to significantly reduce bacterial load and cytokines (TNF-α, IL-6; <i>P</i> < 0.05) with a low probability of resistance via bacterial membrane physical destruction and formation of intracellular ROS. Combined, the results show that a triplet-tryptophan-pivot peptide containing a pair of serine residues was an excellent pathogen-selective candidate for medical devices and was potentially useful in food preservation, crop protection, and human health.