Probiotics Antimicrob Proteins. 2025 Nov 18. doi: 10.1007/s12602-025-10845-3. Online ahead of print.
ABSTRACT
The global rise of multidrug-resistant (MDR) pathogens, particularly Staphylococcus aureus, necessitates the development of novel antimicrobial approaches. Peptidoglycan Recognition Protein-S (PGRP-S), an innate immune effector, is known to target bacterial cell walls by recognizing and hydrolyzing peptidoglycans. Camel (Camelus dromedarius) milk, renowned for its medicinal properties, is a rich source of PGRP-S and contributes to neonatal immunity. This study investigates the antimicrobial and immunomodulatory effects of camel milk-derived PGRP-S (C-PGRP-S) against S. aureus. Purified C-PGRP-S exhibited potent antibacterial activity, completely inhibiting bacterial growth at 40 μg/mL in MIC assays and demonstrating rapid bactericidal action in time-kill kinetics. Scanning electron microscopy revealed dose-dependent morphological damage to bacterial membranes. Immunologically, C-PGRP-S suppressed the overproduction of pro-inflammatory cytokines and restored ROS production in M1 macrophages significantly in infected cells. These results suggest that C-PGRP-S operates via a dual mechanism: direct bacterial lysis and immune modulation. Structural insights from the crystallographic model of camel PGRP-S (PDB ID: 3NW3) further highlight its molecular interaction with peptidoglycans. Taken together, C-PGRP-S emerges as a promising macromolecular therapeutic candidate, with potential as a natural alternative or adjunct to existing antibiotics in managing drug-resistant S. aureus infections.
PMID:41252086 | DOI:10.1007/s12602-025-10845-3
