pH-Dependent Metal Ion Toxicity Influences the Antibacterial Activity of Two Natural Mineral Mixtures
pH-Dependent Metal Ion Toxicity Influences the Antibacterial Activity of Two Natural Mineral Mixtures
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DOI：
10.1371/journal.pone.0009456
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发表时间：
2010-03-01
期刊：
影响因子：
3.7
通讯作者：
Haydel, Shelley E.
中科院分区：
文献类型：
--
作者：
Cunningham, Tanya M.;Koehl, Jennifer L.;Haydel, Shelley E.
背景：最近的研究表明，一些药用矿产品具有抗菌活性，但对抗菌活性所涉及的物理化学性质知之甚少。方法/主要发现：通过体外矿物悬浮液测试，我们鉴定了两种天然矿物混合物，任意命名为BY07和CB07，对广谱细菌病原体具有抗菌活性。矿物衍生的水浸出液也表现出抗菌活性，表明化学而非物理矿物特性对所观察到的活性负责。通过测试金属螯合剂、羟基自由基清除剂、硫脲和不同pH值下的抗菌活性，探讨了对大肠杆菌杀菌活性所必需的化学性质。BY07矿物与EDTA或去铁胺的螯合作用分别消除或降低了BY07的毒性，表明酸溶性金属物种，特别是铁（3+）或其他隔离的金属阳离子在矿物毒性中的作用。这一结论得到了核磁共振弛豫数据的支持，该数据表明，BY07和CB07浸出液中化学可接近的金属离子浓度高于非杀菌矿物样品的浸出液。结论/意义：我们得出结论，水合矿物的酸性环境通过增加金属离子的可用性和毒性显著地促进了抗菌活性。这些发现为进一步研究矿产品的生理作用及其在抗菌辅助治疗中的应用提供了动力。
Background: Recent studies have demonstrated that several mineral products sold for medicinal purposes demonstrate antimicrobial activity, but little is known about the physicochemical properties involved in antibacterial activity.Methodology/Principal Findings: Using in vitro mineral suspension testing, we have identified two natural mineral mixtures, arbitrarily designated BY07 and CB07, with antibacterial activity against a broad-spectrum of bacterial pathogens. Mineral-derived aqueous leachates also exhibited antibacterial activity, revealing that chemical, not physical, mineral characteristics were responsible for the observed activity. The chemical properties essential for bactericidal activity against Escherichia coli were probed by testing antibacterial activity in the presence of metal chelators, the hydroxyl radical scavenger, thiourea, and varying pH levels. Chelation of the BY07 minerals with EDTA or desferrioxamine eliminated or reduced BY07 toxicity, respectively, suggesting a role of an acid-soluble metal species, particularly Fe(3+) or other sequestered metal cations, in mineral toxicity. This conclusion was supported by NMR relaxation data, which indicated that BY07 and CB07 leachates contained higher concentrations of chemically accessible metal ions than leachates from non-bactericidal mineral samples.Conclusions/Significance: We conclude that the acidic environment of the hydrated minerals significantly contributes to antibacterial activity by increasing the availability and toxicity of metal ions. These findings provide impetus for further investigation of the physiological effects of mineral products and their applications in complementary antibacterial therapies.