Faculty of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya, Terrassa, Barcelona 08222, Spain.
ACS Appl Mater Interfaces. 2021 May 19;13(19):22098-22109. doi: 10.1021/acsami.0c16921. Epub 2021 May 4.
The emergence of bacteria resistant to antibiotics and the resulting infections are increasingly becoming a public health issue. Multidrug-resistant (MDR) bacteria are responsible for infections leading to increased morbidity and mortality in hospitals, prolonged time of hospitalization, and additional burden to financial costs. Therefore, there is an urgent need for novel antibacterial agents that will both treat MDR infections and outsmart the bacterial evolutionary mechanisms, preventing further resistance development. In this study, a green synthesis employing nontoxic lignin as both reducing and capping agents was adopted to formulate stable and biocompatible silver-lignin nanoparticles (NPs) exhibiting antibacterial activity. The resulting silver-lignin NPs were approximately 20 nm in diameter and did not agglomerate after one year of storage at 4 °C. They were able to inhibit the growth of a panel of MDR clinical isolates, including , , , , and , at concentrations that did not affect the viability of a monocyte-derived THP-1 human cell line. Furthermore, the exposure of silver-lignin NPs to the THP-1 cells led to a significant increase in the secretion of the anti-inflammatory cytokine IL-10, demonstrating the potential of these particles to act as an antimicrobial and anti-inflammatory agent simultaneously. genes linked with efflux, heavy metal resistance, capsular biosynthesis, and quorum sensing were investigated for changes in gene expression upon sublethal exposure to the silver-lignin NPs. Genes encoding for membrane proteins with an efflux function were upregulated. However, all other genes were membrane proteins that did not efflux metals and were downregulated.
细菌对抗生素的耐药性的出现以及由此导致的感染,正日益成为一个公共卫生问题。多药耐药(MDR)细菌可导致医院感染,增加发病率和死亡率,延长住院时间,并增加医疗费用负担。因此,我们迫切需要新型的抗菌药物,既能治疗 MDR 感染,又能智取细菌的进化机制,防止进一步产生耐药性。在这项研究中,采用了一种绿色合成方法,使用无毒的木质素作为还原剂和封端剂,来制备具有抗菌活性的稳定且生物相容的银-木质素纳米颗粒(NPs)。所得的银-木质素 NPs 的直径约为 20nm,在 4°C 下储存一年后也没有聚集。它们能够抑制一组 MDR 临床分离株的生长,包括 、 、 、 、 ,其浓度在不影响单核细胞衍生的 THP-1 人细胞系活力的情况下,能够抑制细菌生长。此外,银-木质素 NPs 暴露于 THP-1 细胞后,抗炎细胞因子 IL-10 的分泌显著增加,这表明这些颗粒有可能同时作为一种抗菌和抗炎剂发挥作用。研究了与外排、重金属抗性、荚膜生物合成和群体感应相关的 基因在亚致死浓度的银-木质素 NPs 暴露下的基因表达变化。具有外排功能的膜蛋白编码基因被上调。然而,其他所有基因都是不排外泌体的膜蛋白,其表达被下调。