Copper nanoparticles have negligible direct antibacterial impact
Copper nanoparticles have negligible direct antibacterial impact
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DOI：
10.1016/j.impact.2019.100192
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发表时间：
2020-01-01
期刊：
影响因子：
4.9
通讯作者：
Powell, Jonathan J.
中科院分区：
文献类型：
--
作者：
Bastos, Carlos A. P.;Faria, Nuno;Powell, Jonathan J.
简介：可被细菌获得的可溶性铜是有毒的，因此具有抗菌性。无论是纳米结构的铜材料，在分散或团聚的形式，具有抗菌的影响，除了他们的溶解产物，是不清楚的，并在此addressed.Methods：我们采取了五个纳米结构的铜材料，两个金属，和三个氧代氢氧化物与这些被硅酸盐取代。四聚体在细菌生长培养基中，而硅酸盐取代的材料保持分散和小（6.5 nm直径）。对大肠杆菌的抗菌活性。用随时间测量的铜相分布评估大肠杆菌。使用可溶性铜的剂量和基准剂量非线性回归建模，我们确定了该阶段预测抗微生物活性的程度。最后，我们使用了飞行时间二次离子质谱仪，（ToF-SIMS）分析以研究铜的膜粘附作用是否合理或者细胞内摄取是否最可能解释铜的细菌影响。随着时间的推移，对含水材料的颗粒或可溶相的抗微生物活性的比较清楚地表明，可溶性铜而不是颗粒形式与细菌的抑制有关。增长事实上，基准剂量模型显示，导致大肠杆菌减少50%所需的可溶性剂量。对于所有颗粒制剂，在14.5 mg/L（10-19 mg/L 90%置信区间）下，大肠杆菌生长强烈聚集。相比之下，与相同的生存力降低相关的总铜水平变化很大（45-549 mg/L）。最后，为了支持这种可溶性产物在抗微生物活性方面的优势，铜与细菌膜具有低关联性（可溶性和颗粒物质都可以），但细菌内水平很高（只有可溶性铜才能做到）。结论：总之，我们的数据表明，它是可溶性的，而不是颗粒状的铜的摄取，和细胞内负荷不仅接触和膜缔合，使铜对细菌产生毒性。新型抗菌铜化合物的治疗策略应考虑这些发现。
Introduction: Soluble copper that can be acquired by bacteria is toxic and therefore antimicrobial. Whether nanostructured copper materials, in either disperse or agglomerated form, have antimicrobial impact, aside from that of their dissolution products, is not clear and was herein addressed.Methods: We took five nanostructured copper materials, two metallic, and three oxo-hydroxides with one of these being silicate-substituted. Four agglomerated in the bacterial growth media whilst the silicate-substituted material remained disperse and small (6.5 nm diameter). Antibacterial activity against E. coli was assessed with copper phase distribution measured over time. Using the dose of soluble copper, and benchmark dose non-linear regression modelling, we determined how well this phase predicted antimicrobial activity. Finally, we used Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis to investigate whether membrane adhesion effects by copper were plausible or if intracellular uptake most likely explained the bacterial impact of copper.Results: Comparison over time of antimicrobial activity against particulate or soluble phases of the aquated materials clearly demonstrated that soluble copper but not particulate forms were associated with inhibition of bacterial growth. Indeed, the benchmark dose modelling showed the soluble dose required to cause a 50% reduction in E. coli growth was strongly clustered - for all particle formulations - at 14.5 mg/L (10-19 mg/L 90% confidence interval). By comparison, total copper levels associated with the same reduction in viability varied widely (45-549 mg/L). Finally, in favour of this soluble product dominance in terms of antimicrobial activity, copper had low association with bacterial membrane (something both soluble and particulate materials could do) but showed high intra-bacterial levels (something only soluble copper could do).Conclusion: Taken together our data show that it is the uptake of soluble but not particulate copper, and the intracellular loading not just contact and membrane association, that drives copper toxicity to bacteria. Therapeutic strategies for novel antimicrobial copper compounds should consider these findings.