银纳米颗粒对金黄色葡萄球菌具有很高的细胞内和细胞外杀伤作用。
Silver nanoparticles present high intracellular and extracellular killing against Staphylococcus aureus.
机构信息
Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV, USA.
Department of Mechanical Engineering, University of Manitoba, Winnipeg, Canada.
出版信息
J Antimicrob Chemother. 2019 Jun 1;74(6):1578-1585. doi: 10.1093/jac/dkz053.
OBJECTIVES
Bone and joint infections caused by Staphylococcus aureus are becoming increasingly difficult to treat due to rising antibiotic resistance, resilient biofilms and intracellular survival of S. aureus. It has been challenging to identify and develop antimicrobial agents that can be used to kill extracellular and intracellular bacteria while having limited toxicity towards host cells. In addressing this challenge, this study investigates the antimicrobial efficacy and toxicity of silver nanoparticles (AgNPs).
METHODS
Intracellular bacteria were generated using a co-culture model of human osteoblast cells and S. aureus. Extracellular and intracellular S. aureus were treated with AgNPs, antibiotics and their combinations, and numbers of colonies were quantified. Toxicity of AgNPs against human osteoblast cells was determined by quantifying the number of viable cells after treatment.
RESULTS
AgNPs demonstrated excellent antimicrobial activity against extracellular S. aureus with a 100% killing efficacy at concentrations as low as 56 μM, along with a high intracellular killing efficacy of 76% at 371 μM. AgNPs were non-toxic or slightly toxic towards human osteoblasts at the concentrations studied (up to 927 μM). Moreover, smaller-sized (40 nm) AgNPs were more efficacious in killing bacteria compared with their larger-sized (100 nm) counterparts and synergistic antimicrobial effects against extracellular bacteria were observed when AgNPs were combined with gentamicin.
CONCLUSIONS
AgNPs and their combination with antibiotics have demonstrated high extracellular and intracellular bacterial killing and presented unique aspects for potential clinical applications, especially for chronic and recurrent infections where intracellular bacteria may be the cause.
目的
由于金黄色葡萄球菌（Staphylococcus aureus）对抗生素的耐药性不断上升、生物膜具有弹性以及其能够在细胞内生存，由其引起的骨和关节感染越来越难以治疗。目前，人们一直难以确定并开发出既能杀死细胞外和细胞内细菌，又对宿主细胞毒性有限的抗菌药物。为了解决这一挑战，本研究调查了银纳米颗粒（AgNPs）的抗菌功效和毒性。
方法
使用人成骨细胞和金黄色葡萄球菌的共培养模型产生细胞内细菌。用 AgNPs、抗生素及其组合处理细胞外和细胞内金黄色葡萄球菌，并对细菌集落数量进行定量。通过处理后活细胞数量来确定 AgNPs 对人成骨细胞的毒性。
结果
AgNPs 对细胞外金黄色葡萄球菌具有极好的抗菌活性，在低至 56 μM 的浓度下即可达到 100%的杀菌效果，在 371 μM 的浓度下对细胞内金黄色葡萄球菌的杀菌效果高达 76%。在研究浓度（高达 927 μM）下，AgNPs 对人成骨细胞无毒性或毒性轻微。此外，与较大尺寸（100nm）的 AgNPs 相比，较小尺寸（40nm）的 AgNPs 更能有效地杀死细菌，并且当 AgNPs 与庆大霉素联合使用时，观察到对抗细胞外细菌的协同抗菌作用。
结论
AgNPs 及其与抗生素的组合表现出对细胞外和细胞内细菌的高效杀灭作用，并呈现出独特的潜在临床应用前景，特别是对于可能由细胞内细菌引起的慢性和复发性感染。
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