摘要
细菌对碳青霉烯类抗生素耐药性的日益增加,已成为一个备受关注的问题.联合治疗是应对耐药细菌感染的有效策略.在本研究中,双金属纳米颗粒(AuRh NPs)与小分子抗生素(亚胺培南)具有协同抗菌作用,它们通过增加细菌胞内的活性氧水平和增强细菌膜的渗透性表现出优异的抗菌效果.特别地,联合治疗恢复了亚胺培南对耐碳青霉烯类肺炎克雷伯菌(CRKP)的疗效,最低抑菌浓度降低了128倍.在治疗肺部感染时,AuRh NPs与亚胺培南联合使用能更有效地抑制CRKP感染,与单独使用亚胺培南或AuRh NPs实验组相比,小鼠的存活率提升了50%.体外和体内安全性研究表明,AuRh NPs与亚胺培南联合使用没有明显的毒性.这种联合疗法为耐药细菌感染提供了有效的治疗策略.
Increasing resistance to carbapenem antibiotics has become a particular concern.Combination therapy might constitute an effective way to control drug-resistant bacterial infections.Here,we show that AuRh nanoparticles(NPs)have a synergistic antibacterial effect with a small-molecule antibiotic(imipenem),and they exhibit excellent antibacterial efficacies by increasing intracellular reactive oxygen species levels and enhancing the permeability of the bacterial membrane.In particular,the combination therapy restores the efficacy of imipenem against carbapenem-resistant Klebsiella pneumoniae(CRKP),with a 128-fold reduction in the minimum inhibitory concentration.In the treatment of lung infections,the combination of AuRh NPs(2 mg kg^(−1))and imipenem(2 mg kg^(−1))more effectively inhibits CRKP infection,with a 50%increase in the survival rate of mice compared with groups treated with imipenem or AuRh NPs alone.For in vitro and in vivo safety studies,AuRh NPs combined with imipenem show no significant toxicity,even at an injected concentration of 100 mg kg^(−1) in mice.This combination therapeutic provides an effective treatment for drug-resistant bacterial infections.
作者
赵晓慧
刘绍琴
蒋兴宇
Xiaohui Zhao;Shaoqin Liu;Xingyu Jiang(School of Life Science and Technology,Harbin Institute of Technology,Harbin 150001,China;Shenzhen Key Laboratory of Smart Healthcare Engineering,Guangdong Provincial Key Laboratory of Advanced Biomaterials,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen 518055,China)
基金
financially supported by the National Key R&D Program of China(2020YFA0908900,2018YFA0902600,2022YFB3804700,and 2021YFF1200100)
the National Natural Science Foundation of China(22234004)
Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003)
Shenzhen Science and Technology Program(KQTD20190929172743294 and JCYJ20200109141231365)
Shenzhen Key Laboratory of Smart Healthcare Engineering(ZDSYS20200811144003009)
the Natural Science Foundation of Shenzhen City(JCYJ20190809115005628)
Guangdong Innovative and Entrepreneurial Research Team Program(2019ZT08Y191)
Guangdong Major Talent Introduction Project(2019CX01Y196)
the Tencent Foundation through the XPLORER PRIZE for financial support。
