Proteoglycan 4 Does Not Exhibit Direct Bactericidal Activity Against Established Cultures of Escherichia Coli

Proteoglycan 4 (PRG4, lubricin) is a glycoprotein serving as a boundary lubricant in joints and immune-privileged tissues. Although PRG4 coatings prevent bacterial adhesion, potential bactericidal activity remains unclear. Given that antimicrobial heparin-binding peptides act via membrane disruption, the C-terminal heparin-binding region of PRG4 may possess similar properties. We tested full-length PRG4 (PRG4-F) and its C-terminal fragment (PRG4-C) generated by tryptase in a post-infection E. coli killing assay across 5–50 µg/mL. Neither PRG4-F nor PRG4-C reduced bacterial viability, indicating absence of direct bactericidal activity. PRG4’s antimicrobial function therefore appears limited to anti-adhesion mechanisms. Despite structural similarities to antimicrobial peptides, PRG4-C likely lacks amphipathicity required for membrane disruption, a feature that may minimize host cytotoxicity in immune-privileged tissues.