School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an, 710021, China.
University of Alberta, Edmonton, Alberta, Canada.
Int J Antimicrob Agents. 2023 May;61(5):106794. doi: 10.1016/j.ijantimicag.2023.106794. Epub 2023 Mar 16.
Pseudomonas aeruginosa is one of the most common pathogens that lead to fatal human infection. This Gram-negative pathogen has evolved complex drug resistance, which poses significant challenges to the current antibiotic-dependent healthcare system. New therapeutic approaches are urgently required to treat infections caused by P. aeruginosa.
Inspired by ferroptosis, the antibacterial effects of iron compounds on P. aeruginosa via direct exposure were investigated. In addition, thermal-responsive hydrogels to carry FeCl were developed as a wound dressing to treat P. aeruginosa-induced wound infection in a mouse model.
The results showed that 200 µM FeCl killed more than 99.9% of P. aeruginosa cells. FeCl-mediated cell death in P. aeruginosa was associated with hallmarks of ferroptosis in mammalian cells, including reactive oxygen species (ROS) burst, lipid peroxidation, and DNA damage. Catalase or Fe chelator alleviated FeCl-mediated cell death, indicating that HO and labile Fe induced the Fenton reaction leading to cell death. Further proteomics analysis showed that proteins related to glutathione (GSH) synthesis and the glutathione peroxidase (GPX) family were significantly downregulated after FeCl treatment, which is equivalent to GPX4 inactivation in mammalian cells. The therapeutic effect of FeCl on P. aeruginosa was further evaluated in a mouse wound infection model using polyvinyl alcohol-boric acid (PB) hydrogels as a carrier of FeCl. FeCl-PB hydrogels completely cleared pus on wounds and promoted wound healing.
These results indicated that FeCl induces microbial ferroptosis in P. aeruginosa and has high therapeutic potential for the treatment of P. aeruginosa wound infection.
铜绿假单胞菌是导致人类致命感染的最常见病原体之一。这种革兰氏阴性病原体已经进化出复杂的耐药性，这对当前依赖抗生素的医疗保健系统构成了重大挑战。迫切需要新的治疗方法来治疗铜绿假单胞菌引起的感染。
受铁死亡的启发，研究了铁化合物通过直接暴露对铜绿假单胞菌的抗菌作用。此外，还开发了热响应水凝胶来携带 FeCl，作为一种伤口敷料，以治疗小鼠模型中铜绿假单胞菌引起的伤口感染。
结果表明，200µM FeCl 杀死了超过 99.9%的铜绿假单胞菌细胞。FeCl 介导的铜绿假单胞菌细胞死亡与哺乳动物细胞中铁死亡的特征有关，包括活性氧 (ROS) 爆发、脂质过氧化和 DNA 损伤。过氧化氢酶或铁螯合剂减轻了 FeCl 介导的细胞死亡，表明 HO 和不稳定铁诱导芬顿反应导致细胞死亡。进一步的蛋白质组学分析表明，FeCl 处理后与谷胱甘肽 (GSH) 合成和谷胱甘肽过氧化物酶 (GPX) 家族相关的蛋白质显著下调，这相当于哺乳动物细胞中 GPX4 的失活。使用聚乙烯醇-硼酸 (PB) 水凝胶作为 FeCl 的载体，进一步在小鼠伤口感染模型中评估了 FeCl 对铜绿假单胞菌的治疗效果。FeCl-PB 水凝胶完全清除了伤口上的脓液并促进了伤口愈合。
这些结果表明，FeCl 诱导铜绿假单胞菌中的微生物铁死亡，并且对治疗铜绿假单胞菌伤口感染具有很高的治疗潜力。
