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Unearthing the Antibacterial Mechanism of Medicinal Clay: A Geochemical Approach to Combating Antibiotic Resistance

机译:发掘药用粘土的抗菌机制:对抗抗生素耐药性的地球化学方法

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摘要

Natural antibacterial clays, when hydrated and applied topically, kill human pathogens including antibiotic resistant strains proliferating worldwide. Only certain clays are bactericidal; those containing soluble reduced metals and expandable clay minerals that absorb cations, providing a capacity for extended metal release and production of toxic hydroxyl radicals. Here we show the critical antibacterial components are soluble Fe2+ and Al3+ that synergistically attack multiple cellular systems in pathogens normally growth-limited by Fe supply. This geochemical process is more effective than metal solutions alone and provides an alternative antibacterial strategy to traditional antibiotics. Advanced bioimaging methods and genetic show that Al3+ misfolds cell membrane proteins, while Fe2+ evokes membrane oxidation and enters the cytoplasm inflicting hydroxyl radical attack on intracellular proteins and DNA. The lethal reaction precipitates Fe3+-oxides as biomolecular damage proceeds. Discovery of this bactericidal mechanism demonstrated by natural clays should guide designs of new mineral-based antibacterial agents.
机译:天然抗菌粘土经过水合和局部施用后,可杀死人类病原体,包括在全球范围内扩散的抗生素抗性菌株。只有某些黏土具有杀菌作用。那些含有可溶性还原金属和吸收阳离子的可膨胀粘土矿物质,提供了延长金属释放和产生有毒羟基自由基的能力。在这里,我们显示了关键的抗菌成分是可溶性Fe 2 + 和Al 3 + ,它们协同攻击通常受铁供应限制的病原体中的多个细胞系统。这种地球化学过程比单独使用金属溶液更有效,并且为传统抗生素提供了另一种抗菌策略。先进的生物成像方法和遗传学表明,Al 3 + 会错误折叠细胞膜蛋白,而Fe 2 + 会引起膜氧化并进入细胞质,对细胞内的蛋白质和DNA造成羟基自由基攻击。随着生物分子的破坏,致命反应会沉淀出Fe 3 + 氧化物。由天然粘土证明的这种杀菌机理的发现应指导新的基于矿物的抗菌剂的设计。

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