A rapid screening assay for identifying mycobacteria targeted nanoparticle antibiotics

A rapid screening assay for identifying mycobacteria targeted nanoparticle antibiotics
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DOI:
10.3109/17435390.2015.1124468
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发表时间:
2016-01-01
期刊:
影响因子:
5
通讯作者:
Stone, Vicki
Stone, Vicki
中科院分区:
医学3区
文献类型:
--
作者:
Donnellan, Samantha;Tran, Lang;Stone, Vicki

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抗生素耐药性是一个严重的问题。纳米技术在医学上提供了巨大的潜力,但是关于纳米颗粒(NP)对导致严重人类疾病(例如结核病(TB)和麻风病)的分枝杆菌物种的毒性的知识有限。分枝杆菌病是一个主要的全球性健康问题,结核分枝杆菌(Mtb)引起的结核病每年造成200万人死亡,麻风分枝杆菌(M leprae)引起的麻风病每年超过20万例。麻风)。很少有药物对这些分枝杆菌有效,而抗生素耐药性的增加加剧了这一问题。因此,迫切需要替代疗法,但目前用于评估针对分枝杆菌的治疗剂的有效性的大多数测定方法缓慢且昂贵。本研究旨在建立一种快速、低成本的方法,用于筛选化合物对致病性分枝杆菌的抗菌活性,并评估三种NP的毒性(银[Ag]、氧化铜[Cu(II)O]和氧化锌[ZnO])对鸟分枝杆菌副结核亚种的绿色荧光蛋白报道菌株的作用,在反刍动物中引起副结核病的病原性分枝杆菌。使用荧光来监测分支杆菌随时间的生长,NP浓度为6.25-100 μ g/mL,测试长达7天,并设计了一种数据分析方法来比较结果。分枝杆菌对NP的敏感性被认为是NP组合物特异性的,并且毒性可以按以下顺序排列:Ag>Cu(II)O>ZnO。
Antibiotic resistance is a serious problem. Nanotechnology offers enormous potential in medicine, yet there is limited knowledge regarding the toxicity of nanoparticles (NP) for mycobacterial species that cause serious human diseases (e.g. tuberculosis (TB) and leprosy). Mycobacterial diseases are a major global health problem; TB caused by Mycobacterium tuberculosis (Mtb) kills up to 2 million people annually and there are over 200 000 leprosy cases each year caused by Mycobacterium leprae (M. leprae). Few drugs are effective against these mycobacteria and increasing antibiotic resistance exacerbates the problem. As such, alternative therapies are urgently needed but most current assays used to assess the effectiveness of therapeutics against mycobacteria are slow and expensive. This study aimed to develop a rapid, low-cost assay which can be used for screening the antimicrobial properties of compounds against pathogenic mycobacteria and to assess the toxicity of three NP (silver [Ag], copper oxide [Cu(II)O], and zinc oxide [ZnO]) against a green fluorescent protein reporter strain of Mycobacterium avium subspecies paratuberculosis, a slow growing, pathogenic mycobacterial species causing paratuberculosis in ruminants. Fluorescence was used to monitor mycobacterial growth over time, with NP concentrations of 6.25-100 mu g/mL tested for up to 7 days, and a method of data analysis was designed to permit comparison between results. Mycobacterial sensitivity to the NP was found to be NP composition specific and toxicity could be ranked in the following order: Ag>Cu(II)O>ZnO.