Abstract
Pseudomonas aeruginosa (PA), a gram-negative opportunistic pathogen, poses severe risks to immunocompromised patients. Conventional antibiotics often fail due to toxicity and resistance, primarily linked to biofilm formation controlled by quorum sensing (QS). Here, we developed an AidH-loaded sulfonated polyetheretherketone (AidH@SPEEK) composite, optimizing its loading conditions (400 μL AidH, 30 min). Enzymatic activity peaked at 40°C and pH 7.0 but remained stable at 37°C. AidH@SPEEK significantly suppressed PA biofilm formation and virulence factor secretion while downregulating QS (LasR/LasI, RhlR/RhlI) and virulence genes (exoS, phzM). Notably, it enhanced PA's antibiotic susceptibility, offering a promising QS-targeting strategy to combat resistant infections. IMPORTANCE: The rising antibiotic resistance in Pseudomonas aeruginosa (PA) underscores the urgent need for alternative therapeutic approaches. This study highlights the potential of AidH@SPEEK as a non-antibiotic strategy to combat PA infections by targeting the quorum-sensing (QS) system, a key regulator of biofilm formation and virulence. By degrading QS signaling molecules, AidH@SPEEK disrupts bacterial communication, reduces pathogenicity, and enhances antibiotic sensitivity. The use of SPEEK as a delivery platform ensures sustained enzyme activity and biocompatibility, making it suitable for medical implants. These findings offer a promising direction for developing anti-infective materials that mitigate biofilm-associated resistance, ultimately improving clinical outcomes for high-risk patients.