Multifunctional Antimicrobial Polypeptide-Selenium Nanoparticles Combat Drug-Resistant Bacteria
Multifunctional Antimicrobial Polypeptide-Selenium Nanoparticles Combat Drug-Resistant Bacteria
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DOI：
10.1021/acsami.0c17550
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发表时间：
2020-12-16
影响因子：
9.5
通讯作者：
O'Connor, Andrea J.
中科院分区：
文献类型：
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作者：
Huang, Tao;Holden, James A.;O'Connor, Andrea J.
耐药细菌对人类健康构成严重威胁。世界卫生组织的全球抗菌药物监测系统显示，22个国家的50万患者普遍存在抗生素耐药性，其中金黄色葡萄球菌、大肠杆菌和肺炎克雷伯菌是最常见的耐药菌种。抗菌纳米颗粒正在成为对抗抗菌素耐药性的抗生素的有前途的替代品。在这项工作中，合成了涂有抗菌多肽ε-聚-L-赖氨酸（Se NP-ε-PL）的硒纳米粒子，并研究了其抗菌活性和细胞毒性。 Se NP-epsilon-PL 对所有八种测试的细菌（包括革兰氏阳性菌、革兰氏阴性菌和耐药菌株）表现出比其单独成分 Se NP 和 epsilon-PL 显着更高的抗菌活性。纳米颗粒在最低抑制浓度下对人真皮成纤维细胞没有毒性，显示出治疗窗口。此外，与传统抗生素卡那霉素不同，Se NP-epsilon-PL 不易诱导大肠杆菌或金黄色葡萄球菌产生耐药性。具体而言，金黄色葡萄球菌从大约44代开始产生对卡那霉素的抗性，而大约需要132代才产生对Se NP-ε-PL的抗性。令人惊讶的是，大肠杆菌在近 300 代的时间内未能对纳米粒子产生耐药性。这些结果表明，将Se NP与ε-PL结合形成Se NP-ε-PL的多功能方法是一种高效的新策略，具有广谱抗菌活性、低细胞毒性和显着延迟耐药性的发展。
Antibiotic-resistant bacteria are a severe threat to human health. The World Health Organization's Global Antimicrobial Surveillance System has revealed widespread occurrence of antibiotic resistance among half a million patients across 22 countries, with Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae being the most common resistant species. Antimicrobial nanoparticles are emerging as a promising alternative to antibiotics in the fight against antimicrobial resistance. In this work, selenium nanoparticles coated with the antimicrobial polypeptide, epsilon-poly-L-lysine, (Se NP-epsilon-PL) were synthesized and their antibacterial activity and cytotoxicity were investigated. Se NP-epsilon-PL exhibited significantly greater antibacterial activity against all eight bacterial species tested, including Gram-positive, Gram-negative, and drug-resistant strains, than their individual components, Se NP and epsilon-PL. The nanoparticles showed no toxicity toward human dermal fibroblasts at the minimum inhibitory concentrations, demonstrating a therapeutic window. Furthermore, unlike the conventional antibiotic kanamycin, Se NP-epsilon-PL did not readily induce resistance in E. coli or S. aureus. Specifically, S. aureus began to develop resistance to kanamycin from similar to 44 generations, whereas it took similar to 132 generations for resistance to develop to Se NP-epsilon-PL. Startlingly, E. coli was not able to develop resistance to the nanoparticles over similar to 300 generations. These results indicate that the multifunctional approach of combining Se NP with epsilon-PL to form Se NP-epsilon-PL is a highly efficacious new strategy with wide-spectrum antibacterial activity, low cytotoxicity, and significant delays in development of resistance.