Ferroptosis-mediated intestinal decolonization of Klebsiella pneumoniae using Fe/PPy nanomaterials under near-infrared light

Introduction Klebsiella pneumoniae (KP) is a Gram-negative bacterium with a thick capsule that confers natural drug resistance, making it a common opportunistic pathogen. In recent years, the spread of hypervirulent Klebsiella pneumoniae (hvKP) and carbapenem-resistant Klebsiella pneumoniae (CR-KP) strains has created major treatment challenges. Among these, of particular concern is carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), which combines both hypervirulence and carbapenem resistance. This strain can persistently colonize the gut, facilitating resistance gene spread and causing bacterial translocation with subsequent infections. CR-hvKP has now become a key pathogen in both hospital and community settings. Traditional antibiotic treatments often lead to the emergence of bacterial resistance, necessitating the development of novel antimicrobial strategies. Methods This study introduces an iron-polypyrrole nanocomposite (Fe/PPy) designed to leverage an innovative mechanism of ferroptosis-induced bacterial killing. The nanomaterial possesses intrinsic Fenton reaction activity. Moreover, its photothermal conversion efficiency exceeds 85%. Under 1,064 nm near-infrared (NIR) light, its photothermal effect significantly enhances the Fenton reaction efficiency, thereby effectively catalyzing the conversion of bacterial endogenous H₂O₂ into reactive oxygen species (ROS), thereby inducing bacterial lipid peroxidation and achieving targeted bacterial killing via the ferroptosis pathway. Results The excellent tissue penetration of 1,064 nm NIR light enables this material to act precisely on deep-seated infectious lesions, achieving in vivo antibacterial efficacy. Experimental results demonstrate that Fe/PPy nanomaterials exhibit high antimicrobial efficacy and safety against KP without readily inducing bacterial resistance. Discussion This study provides a novel nanodrug design approach for the clinical treatment of KP infections, offering significant translational potential in the field of anti-infective therapy.