The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents.

中文翻译：

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光敏 AIEgens 使细菌对氧化损伤敏感并调节巨噬细胞的炎症反应，以挽救针对 MRSA 的光动力疗法


迫切需要抗菌药物来对抗多重耐药细菌引起的感染，这促进了对替代策略的探索，例如光敏剂（PS）介导的光灭活。然而，越来越多的研究发现，具有相似光动力和病原体靶向特性的 PS 之间的杀菌活性不相关。为了优化针对感染的光动力疗法 (PDT)，我们研究了 D-π-A AIEgens TI、TBI 和 TTI 的三种 I 型 PS。 TI、TBI 和 TTI 产生活性氧 (ROS) 的能力与其杀菌活性不相符。尽管 TI 表现出最低的光动力效率，但通过削弱细菌的抗氧化反应，表现出最高的抗甲氧西林 (MRSA) 活性。相比之下，TTI 的特点是产生最强的 ROS，通过增强巨噬细胞的炎症反应来灭活细胞内 MRSA。与 TI 和 TTI 不同，TBI 尽管具有中等光动力活性并诱导 MRSA 和巨噬细胞中 ROS 积累，但没有表现出任何抗菌活性。因此，依靠扰乱病原体的抗氧化代谢或增强宿主的免疫反应，短暂的ROS爆发可以有效控制细菌感染。我们的研究重新评估了 PS 的光动力活性对细菌消除的贡献，并为发现新的抗菌靶点和药物提供了新的见解。