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

Lingkai Dong1, Xingjin Li2, Tao Hu3

  • 1School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Insights

This study developed a novel coating for medical devices using bacteriophage depolymerases to combat Acinetobacter baumannii infections. The depolymerase-coated surfaces effectively reduced bacterial load and biofilm formation, offering a promising strategy against catheter-related bloodstream infections.

Area of Science:

  • Biotechnology
  • Materials Science
  • Infectious Disease Research

Background:

  • Catheter-related bloodstream infections (CRBSI) pose significant clinical and economic burdens.
  • Emerging trends show Gram-negative bacilli, particularly Acinetobacter baumannii, are increasingly prevalent CRBSI pathogens due to antibiotic resistance and biofilm formation.
  • Bacteriophage depolymerases offer a novel antivirulence strategy by degrading bacterial capsular polysaccharides and exopolysaccharides.

Purpose of the Study:

  • To develop and evaluate a polydopamine (PDA)-coated catheter surface functionalized with an Acinetobacter baumannii-specific depolymerase (DPO71).
  • To assess the antibacterial, antibiofilm, and in vivo efficacy of the DPO71-PDA coating against Acinetobacter baumannii.
  • To determine the coating's stability, robustness, and biocompatibility.

Main Methods:

  • Immobilization of A. baumannii-specific depolymerase DPO71 onto various substrates using a mussel-inspired polydopamine (PDA) coating technique.
  • Evaluation of antibacterial and antibiofilm activity in vitro using human serum, epithelial cell-bacteria co-cultures, and ex vivo blood infection models.
  • Assessment of in vivo efficacy in a mouse subcutaneous implantation model and evaluation of coating stability and biocompatibility using epithelial cells and Galleria mellonella larvae.

Main Results:

  • The DPO71-PDA coating achieved significant surface coverage and demonstrated potent antibacterial and antibiofilm activities in the presence of human serum.
  • The modified surfaces substantially reduced bacterial burden in epithelial cell-bacteria co-culture and ex vivo blood infection models.
  • In vivo studies in mice showed a significant reduction in bacterial load with DPO71-coated implants, alongside good coating robustness, stability, and minimal toxicity.

Conclusions:

  • A simple PDA coating technique effectively immobilizes bacteriophage depolymerases onto diverse surfaces, creating potent antibacterial and antibiofilm properties.
  • Depolymerase-functionalized coatings show significant potential for mitigating Acinetobacter baumannii-associated CRBSI.
  • This approach offers a promising strategy to combat antibiotic-resistant Gram-negative bacterial infections on medical devices.

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