Antibacterial activities and molecular mechanism of amino-terminal fragments from pig nematode antimicrobial peptide CP-1

Abstract

High manufacturing costs and weak cell selectivity have limited the clinical application of naturally occurring peptides when faced with an outbreak of drug-resistance. To overcome these limitations, a set of antimicrobial peptides was synthesized with the general sequence of (WL)n, where n= 1, 2, 3 and WL was truncated from the N-terminus of Cecropin P1 without initial serine residues. The antimicrobial peptide WL3 exhibited stronger antimicrobial activity against both Gram-negative and Gram-positive microbes than the parental peptide CP-1. WL3 showed no hemolysis even at the highest test concentrations compared to the parental peptide CP-1. The Condition sensitivity assays (salts, serum and trypsin) demonstrated that WL3 had high stability in vitro. Fluorescence spectroscopy and electron microscopy indicated that WL3 killed microbes by means of penetrating the membrane and causing cell lysis. In a mouse model, WL3 was able to significantly reduce the bacteria load in major organs and cytokines (TNF-α,IL-6 and IL-1β) levels in serum. In summary, these findings suggest that WL3, which was modified from a natural antimicrobial peptide, has enormous potential for application as a novel antibacterial agent.

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High manufacturing costs and weak antimicrobial activity have limited the application of naturally occurring peptides. In this study, we combined the advantage of peptide truncation and tandem repeat units to generate short Cecropin P1-derived peptides and investigated their antimicrobial activity and model of action. Antimicrobial peptide WL3 has enormous potential for application as a novel antimicrobial agent.

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