Application of a thiophene-based conjugated polymer in the photocatalytic eradication of multidrug-resistant bacteria: Synergistic inactivation of MRSA via carboxyl capture and multi-pathway regulation.

Methicillin-resistant Staphylococcus aureus poses a significant public health risk due to its multidrug resistance mechanism. This study applies a three-in-one antibacterial strategy incorporating "molecular conjugation-photocatalysis-omics analysis" to design and synthesize a thienyl conjugated polymer (YQ). Optimization of the main chain of the polythiophene-alkynyl conjugated system for light capture with electric field regulation by the carboxyl group has delivered dual bactericidal properties under visible light. The system decomposes bacterial cell membranes via oxidation with reactive oxygen species such as hydroxyl radicals (•OH), where 107 CFU/mL of methicillin-resistant Staphylococcus aureus (MRSA) was fully inactivated within 2 h. In vivo experiments further demonstrated that YQ not only exhibited effective antimicrobial activity under visible light irradiation but also promoted the healing of bacteria-infected wounds. Transcriptomics has revealed the YQ sterilization mechanism that involves the energy supply of the tricarboxylic acid cycle, the defense system of ABC transporters, and the repair pathway of branched-chain amino acids, forcing the bacteria into an "energy depletion-defense collapse-repair paralysis" death cycle. This study demonstrates the combined effectiveness of molecular engineering, organic photocatalysts, and the regulation of bacterial metabolic networks. The findings can serve as a theoretical and experimental basis for the application of organic polymer photocatalytic antibacterial agents.