LEAP‐1, a novel highly disulfide‐bonded human peptide, exhibits antimicrobial activity

TLDR

The study reports the isolation and characterization of a novel human peptide, LEAP‑1, with antimicrobial activity. The peptide was identified by mass spectrometry as a 25‑residue, four‑disulfide‑bonded cysteine‑rich peptide from human blood, and its antimicrobial activity was confirmed in radial diffusion assays against various bacteria and yeast. LEAP‑1 is mainly expressed in the liver, shows dose‑dependent antimicrobial activity against Gram‑positive and Gram‑negative bacteria and yeast, and expands the mammalian antimicrobial peptide repertoire with a novel disulfide motif.

Abstract

We report the isolation and characterization of a novel human peptide with antimicrobial activity, termed LEAP‐1 (liver‐expressed antimicrobial peptide). Using a mass spectrometric assay detecting cysteine‐rich peptides, a 25‐residue peptide containing four disulfide bonds was identified in human blood ultrafiltrate. LEAP‐1 expression was predominantly detected in the liver, and, to a much lower extent, in the heart. In radial diffusion assays, Gram‐positive Bacillus megaterium , Bacillus subtilis , Micrococcus luteus , Staphylococcus carnosus , and Gram‐negative Neisseria cinerea as well as the yeast Saccharomyces cerevisiae dose‐dependently exhibited sensitivity upon treatment with synthetic LEAP‐1. The discovery of LEAP‐1 extends the known families of mammalian peptides with antimicrobial activity by its novel disulfide motif and distinct expression pattern.