Nanoscale Structure-Activity Relationships, Mode of Action, and Biocompatibility of Gold Nanoparticle Antibiotics
Nanoscale Structure-Activity Relationships, Mode of Action, and Biocompatibility of Gold Nanoparticle Antibiotics
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DOI：
10.1021/ja408505n
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发表时间：
2014-04-09
影响因子：
15
通讯作者：
Feldheim, Daniel L.
中科院分区：
文献类型：
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作者：
Bresee, Jamee;Bond, Constance M.;Feldheim, Daniel L.
病原菌对多种抗菌素耐药性的出现已成为一个重大的全球公共卫生威胁。由于20多年来没有出现针对革兰氏阴性菌的新型小分子抗生素，多重耐药（MDR）革兰氏阴性菌已成为特别棘手的问题。我们开发了一种组合筛选工艺，用于鉴定具有抗生素活性的混合配体单层/金纳米颗粒偶联物（直径2.4 nm）。该方法先前发现了几种对革兰氏阴性杆菌大肠杆菌具有有效活性的偶联物。在这里，我们表明这些结合物对耐多药大肠杆菌和耐多药肺炎克雷伯菌也有活性。此外，我们已经证明，对这些纳米颗粒的耐药性比对商业小分子药物的耐药性发展要慢得多。这些结果，结合它们对哺乳动物细胞相对较低的毒性和体内生物相容性，表明金纳米颗粒可能是治疗耐多药革兰氏阴性细菌感染的可行的新候选物。
The emergence of resistance to multiple antimicrobial agents by pathogenic bacteria has become a significant global public health threat. Multi-drug-resistant (MDR) Gram-negative bacteria have become particularly problematic, as no new classes of small-molecule antibiotics for Gram-negative bacteria have emerged in over two decades. We have developed a combinatorial screening process for identifying mixed ligand monolayer/gold nanoparticle conjugates (2.4 nm diameter) with antibiotic activity. The method previously led to the discovery of several conjugates with potent activity against the Gram-negative bacterium Escherichia coli. Here we show that these conjugates are also active against MDR E. coli and MDR Klebsiella pneumoniae. Moreover, we have shown that resistance to these nanoparticles develops significantly more slowly than to a commercial small-molecule drug. These results, combined with their relatively low toxicity to mammalian cells and biocompatibility in vivo, suggest that gold nanoparticles may be viable new candidates for the treatment of MDR Gram-negative bacterial infections.