Department of Surgery, Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide , Adelaide, South Australia Australia.
Future Industries Institute, University of South Australia , Mawson Lakes, South Australia Australia.
ACS Appl Mater Interfaces. 2017 Jul 5;9(26):21631-21638. doi: 10.1021/acsami.7b03672. Epub 2017 Jun 23.
Biofilms are aggregates of bacteria residing in a self-assembled matrix, which protects these sessile cells against external stress, including antibiotic therapies. In light of emerging multidrug-resistant bacteria, alternative strategies to antibiotics are emerging. The present study evaluated the activity of colloidal silver nanoparticles (AgNPs) of different shapes against biofilms formed by Staphylococcus aureus (SA), methicillin-resistant SA (MRSA), and Pseudomonas aeruginosa (PA). Colloidal quasi-spherical, cubic, and star-shaped AgNPs were synthesized, and their cytotoxicity on macrophages (THP-1) and bronchial epithelial cells (Nuli-1) was analyzed by the lactate dehydrogenase assay. The antibiofilm activity was assessed in vitro by the resazurin assay and in an in vivo infection model in Caenorhabditis elegans. Cubic and star-shaped AgNPs induced cytotoxicity, while quasi-spherical AgNPs were not toxic. Quasi-spherical AgNPs showed substantial antibiofilm activity in vitro with 96% (±2%), 97% (±1%), and 98% (±1%) biofilm killing of SA, MRSA, and PA, respectively, while significantly reducing mortality of infected nematodes. The in vivo antibiofilm activity was linked to the accumulation of AgNPs in the intestinal tract of C. elegans as observed by 3D X-ray tomography. Quasi-spherical AgNPs were physically stable in suspension for over 6 months with no observed loss in antibiofilm activity. While toxicity and stability limited the utilization of cubic and star-shaped AgNPs, quasi-spherical AgNPs could be rapidly synthesized, were stable and nontoxic, and showed substantial in vitro and in vivo activity against clinically relevant biofilms. Quasi-spherical AgNPs hold potential as pharmacotherapy, for example, as topical treatment for biofilm-related infections.
生物膜是细菌在自组装基质中聚集的产物,它可以保护这些不动细菌免受外部压力,包括抗生素治疗。鉴于新兴的多药耐药细菌,正在出现抗生素的替代策略。本研究评估了不同形状的胶体银纳米颗粒(AgNPs)对金黄色葡萄球菌(SA)、耐甲氧西林金黄色葡萄球菌(MRSA)和铜绿假单胞菌(PA)形成的生物膜的活性。合成了胶体准球形、立方和星形 AgNPs,并通过乳酸脱氢酶测定法分析其对巨噬细胞(THP-1)和支气管上皮细胞(Nuli-1)的细胞毒性。通过 Resazurin 测定法和秀丽隐杆线虫体内感染模型评估了抗生物膜活性。立方和星形 AgNPs 诱导细胞毒性,而准球形 AgNPs 则没有毒性。准球形 AgNPs 在体外具有显著的抗生物膜活性,对 SA、MRSA 和 PA 的生物膜杀伤率分别为 96%(±2%)、97%(±1%)和 98%(±1%),同时显著降低了感染线虫的死亡率。体内抗生物膜活性与在秀丽隐杆线虫肠道中观察到的 AgNPs 积累有关,这可以通过 3D X 射线断层扫描观察到。准球形 AgNPs 在悬浮液中超过 6 个月保持物理稳定,没有观察到抗生物膜活性的丧失。虽然毒性和稳定性限制了立方和星形 AgNPs 的利用,但准球形 AgNPs 可以快速合成,稳定且无毒,并且在体外和体内对临床相关生物膜具有显著的活性。准球形 AgNPs 具有作为药物治疗的潜力,例如,作为治疗生物膜相关感染的局部治疗。