Evolutionarily conserved peptidoglycan recognition proteins mediate antibacterial immunity in planarians

Peptidoglycan recognition proteins (PGRPs) are conserved pattern recognition receptors that mediate bacterial sensing and clearance in vertebrates and arthropods, but their roles in lophotrochozoans remain largely unexplored. Here, we identify and characterize seven PGRPs in the planarian Schmidtea mediterranea, including three secreted (PGRP-S1-S3) and four membrane-associated (PGRP-L1-L4) proteins. Structural modeling demonstrated conserved PGRP domain architecture, and molecular docking predicted interactions with peptidoglycan-derived ligands. S. mediterranea PGRPs (Smed-PGRPs) are enriched in the intestine and epidermis, and are dynamically regulated following injury. Infection with Staphylococcus aureus induced route- and tissue-specific PGRP expression responses. RNA interference-mediated depletion of Smed-PGRPs impaired bacterial clearance, with PGRP-S3 loss resulting in the strongest increase in pathogen persistence and tissue invasion. Together, these findings demonstrate that PGRPs are essential mediators of planarian antibacterial immunity and support the evolutionary conservation of PGRP-mediated antibacterial mechanisms across bilaterian lineages.