Abstract Antibacterial nanomaterials provide promising alternative strategies to combat the global challenge of bacterial infection due to deteriorating resistance. However, few have been applied for intracellular bacteria killing or in vivo therapy due to potential cytotoxicity and poor biocompatibility. Here we present a strategy to generate formula suitable for in vivo anti-infective therapy by decocting antibacterial nanomaterial. An aqueous formula containing ferrous iron and polysulfide (Fe(II)Snaq) is prepared by a decoction procedure using nano-iron sulfide (nFeS) as raw substance. Theoretical calculation indicated that replacement of a sulfur atom by an oxygen atom occurred, resulting in polysulfide release and iron dissolution. The Fe(II)Snaq decocted from nFeS induced bacterial death with ferroptosis-like hallmarks, including iron enrichment, lipid peroxidation, and glutathione (GSH) depletion. The antibacterial action of Fe(II)Snaq was dependent on ferrous iron, which could be inhibited by iron chelators, ferroptosis inhibitors, and GSH, while the polysulfide prevented ferrous iron oxidation and counteracted GSH. Furthermore, Fe(II)Snaq not only killed up to 99 % of planktonic bacteria within 5 min, but also suppressed up to 90 % of intracellular Staphylococcus aureus without triggering cytotoxicity to host cell. Administration of Fe(II)Snaq achieved equivalent therapeutic effect to vancomycin for infectious pneumonia treatment and significantly prolonged the survival period of septic mice. These results indicate that aqueous ferrous polysulfide can induce ferroptosis- like death in bacteria and may be formulated as an antibacterial alternative for anti-infection therapy.

中文翻译：

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纳米煎煮多硫化亚铁协调细菌中铁死亡样死亡用于抗感染治疗

摘要抗菌纳米材料提供了有希望的替代策略，以应对由于耐药性恶化而导致的细菌感染的全球挑战。然而，由于潜在的细胞毒性和较差的生物相容性，很少被应用于细胞内细菌的杀灭或体内治疗。在这里，我们提出了一种通过煎煮抗菌纳米材料来生成适用于体内抗感染治疗的配方的策略。使用纳米硫化铁 (nFeS) 作为原料，通过煎煮程序制备含有亚铁和多硫化物 (Fe(II)Snaq) 的水性配方。理论计算表明，硫原子被氧原子取代，导致多硫化物释放和铁溶解。从 nFeS 中煎出的 Fe(II)Snaq 诱导细菌死亡，具有铁死亡样特征，包括铁富集、脂质过氧化和谷胱甘肽（GSH）消耗。Fe(II)Snaq 的抗菌作用依赖于亚铁，可被铁螯合剂、铁死亡抑制剂和 GSH 抑制，而多硫化物可防止亚铁氧化并抵消 GSH。此外，Fe(II)Snaq 不仅在 5 分钟内杀死了高达 99% 的浮游细菌，而且还抑制了高达 90% 的细胞内金黄色葡萄球菌，而不会引发对宿主细胞的细胞毒性。Fe(II)Snaq 治疗感染性肺炎取得了与万古霉素相当的治疗效果，并显着延长了败血症小鼠的存活期。