Department of Public Health, The Brody School of Medicine, East Carolina University, Greenville, NC, USA.
School of Law, University of California, Berkeley, Berkeley, CA, USA.
Sci Rep. 2022 Apr 25;12(1):6729. doi: 10.1038/s41598-022-10778-9.
To tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH-AgNPs) were bactericidal; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate-AgNPs) were nontoxic; and Ag ions were bacteriostatic forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in E. coli. Further, adherent fimbriae were expressed with Citrate-AgNPs (0.5-10 µg/mL), whereas NH-AgNPs (0.5-10 µg/mL) or Ag ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH-AgNPs treatments, suggesting NH-AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH-AgNPs and the lack of toxicity of Citrate-AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.
为了解决日益严重的抗生素耐药性（AR）和医院获得性感染（HAI）问题，我们需要开发新型的抗菌药物，这些药物不仅要对 HAI 有效，而且对人体更安全。我们假设，具有正电荷且粒径为 5nm 的纳米颗粒可以特异性靶向细菌细胞壁和黏附菌毛的表达，成为下一代抗菌药物。本文研究表明，高度带正电荷、5nm 的氨基功能化银纳米颗粒（NH-AgNPs）具有杀菌作用；高度带负电荷、45nm 的柠檬酸盐功能化 AgNPs（Citrate-AgNPs）无毒性；Ag 离子具有抑菌作用，可形成蜂窝状潜在耐药表型，在大肠杆菌中，Ag 离子浓度为 10μg/mL 时表现出抑菌作用。此外，Citrate-AgNPs（0.5-10μg/mL）可促进黏附菌毛的表达，而 NH-AgNPs（0.5-10μg/mL）或 Ag 离子（仅在 10μg/mL 时）可抑制菌毛的表达。我们的研究结果还表明，NH-AgNPs 处理人肺上皮细胞和真皮成纤维细胞后，不会引起脂质过氧化，提示 NH-AgNPs 具有良好的生物相容性。具有生物相容性的 NH-AgNPs 表现出强大的杀菌作用，而 Citrate-AgNPs 无毒性，这一结果支持了以下假设，即具有小尺寸和正电荷的 AgNPs 可能成为下一代抗菌药物，有望解决日益严重的 HAI 问题，保障患者的健康和安全。
