One‐Step Immobilized Phage Depolymerase Coatings for Catheter‐Related Bloodstream Infections

Abstract

ABSTRACT 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/cm 2 . 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.