One-Step Immobilized Phage Depolymerase Coatings for Catheter-Related Bloodstream Infections.

Catheter-related bloodstream infection (CRBSI) is an important clinical problem that causes significant mortality and excess economic cost. Recent epidemiological trends indicate a shift in CRBSI pathogens from Gram-positive to Gram-negative bacilli, among which Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii predominate due to their strong antibiotic resistance and biofilm-forming capabilities. Recently, bacteriophage-encoded depolymerases have emerged as promising antivirulence agents that resensitize bacteria to host immunity by degrading capsular polysaccharides (CPS) and exopolysaccharides (EPS). In this study, we employed a mussel-inspired polydopamine (PDA) coating technique to immobilize an A. baumannii-specific depolymerase, DPO71, onto diverse organic, inorganic, and metal substrates, with a maximum surface coverage of​ ∼0.2 µg/cm2. In the presence of human serum, DPO71-coated surfaces demonstrated potent antibacterial and antibiofilm activities. The coating significantly reduced bacterial burden in an epithelial cell-bacteria co-culture system and in ex vivo blood infection models. Moreover, DPO71 coatings demonstrated good robustness, stability, and minimal toxicity toward epithelial cells and Galleria mellonella larvae​. Importantly, in a mouse subcutaneous implantation model, the DPO71 coating significantly reduced bacterial load in vivo. Overall, modifying catheter surfaces with depolymerases via a simple PDA coating technique demonstrates great potential in mitigating bacteria-associated CRBSI.