DEFB118 (defensin beta 118) is a host defense peptide expressed predominantly in the male reproductive tract that functions as a multifaceted antimicrobial and immunoregulatory protein 1. The peptide exhibits broad-spectrum antimicrobial activity against both Gram-negative bacteria (E. coli, S. typhimurium) and Gram-positive bacteria (S. aureus, B. subtilis) with minimum inhibitory concentrations of 4 μg/mL 2. Mechanistically, DEFB118 kills bacteria through rapid permeabilization of both outer and inner membranes, causing striking morphological alterations visible by electron microscopy, while sparing eukaryotic cell membranes 1. Beyond direct antimicrobial effects, DEFB118 binds lipopolysaccharides (LPS) with high affinity (KD: 2.94 nM), preventing LPS-mediated inflammatory signaling and reducing production of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) 3. DEFB118 also inhibits E. coli adhesion to intestinal epithelial cells and enhances cell viability during bacterial challenge 2. In vivo, DEFB118 attenuates enterotoxigenic E. coli-induced intestinal inflammation and injury through suppression of NF-κB and TLR4 signaling while promoting tight junction integrity 4. These antimicrobial and anti-inflammatory properties position DEFB118 as a potential therapeutic candidate against antibiotic-resistant bacterial infections and inflammatory bowel diseases.