A conjugated polymer antimicrobial agent triggers metabolic cascade-mediated killing of carbapenem-resistant Klebsiella pneumoniae

Introduction Carbapenem-resistant Klebsiella pneumoniae (CRKP) skin infections represent a critical therapeutic challenge due to biofilm formation and poor drug penetration. Reactive oxygen species (ROS)-mediated strategies, such as advanced photodynamic therapy, offer promising multi-target approaches against such resistant pathogens. Methods We developed a light-tunable conjugated polymer, P3, designed to penetrate CRKP biofilms and achieve spatiotemporally controlled activation. Its efficacy was evaluated against established CRKP biofilms in both dark and visible light conditions, assessing biofilm biomass elimination and bacterial viability. Results P3 leveraged its intrinsic optical properties and ROS production to eliminate 50% of the CRKP biofilm in darkness. Upon visible light irradiation, its efficacy was dramatically enhanced via a triggered compensatory self-destruction (CSD) mechanism. This self-amplifying reaction catastrophically disrupted bacterial membrane integrity and oxidative balance, resulting in the internal destruction of over 80% of the biofilm and bacterial death. This action combines physical matrix breakdown with ROS-mediated biomolecular damage, leading to near-complete biofilm eradication. Discussion Our study demonstrates that P3 functions as a "metabolic time bomb," providing a targeted, antibiotic-free strategy against structured bacterial communities. These findings highlight the significant potential of this light-controlled platform for treating resistant biofilm-associated infections.