D-enantiomeric β-casein 197 disrupts biofilm-associated infection of MDR Pseudomonas aeruginosa and Acinetobacter baumannii through superior LPS binding and host cell protection.

D-enantiomeric β-casein 197 reduces biofilm biomass by up to 88% and improves survival in infection models against MDR Pseudomonas aeruginosa and Acinetobacter baumannii.

• Why it matters: Biofilms formed by MDR P. aeruginosa and A. baumannii cause persistent infections and therapeutic failure, highlighting the need for more effective antibiofilm agents resistant to protease degradation.
• What they did: Researchers synthesized and compared L- and D-β-casein 197, a milk-derived AMP, testing their antibiofilm activity, membrane disruption, LPS binding, and host cell protection across eight clinical isolates and in a Galleria mellonella infection model.
• The result: The D-form demonstrated superior biofilm reduction, membrane disruption, LPS binding affinity (KD 0.8 μM vs 3.1 μM), and host cell protection, significantly improving survival with negligible host toxicity, suggesting its potential as a potent antibiofilm agent.