Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics.
Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics.
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噬菌体尾状颗粒可杀死艰难梭菌，是传统抗生素的替代品。
DOI：
10.1016/j.surg.2014.06.015
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发表时间：
2015
期刊：
影响因子：
3.8
通讯作者：
StewartSr,DavidB
中科院分区：
文献类型：
--
作者：
Sangster,William;Hegarty,JohnP;StewartSr,DavidB
背景目前艰难梭菌感染（CDI）的抗生素治疗方案在达到治愈和预防复发方面变得越来越无效。最近开发的传统抗生素的替代品是噬菌体尾样颗粒（PTLP），这是一种在形态上与噬菌体相似的蛋白质，由艰难梭菌产生。本研究探讨了以前未报道的PTLP分离的临床分离ofC difficile.MethodsUsing患者来源的样品从一个机构审查委员会approvedC difficiletissue银行，核糖体型078 C difficileisolate是厌氧培养的血琼脂板上prewabbed与诺氟沙星诱导生产的PTLP体外杀伤谱。使用透射电子显微镜证实了浓缩的PTLP群体。使用标准菌苔斑点方法，如细菌菌苔内的清除所指示的那样评估杀菌活性。PTLP基因组簇也完全测序和开放的阅读框架进行了注释，根据预测function.ResultsPTLPs进行了评估，使用64 patient-derivedC difficileisolates的不同ribotypes。PTLP在25个核糖体型027分离株中的21个中表现出完全杀菌活性，在25个中的2个中具有部分活性。对任何其他核糖体型或非艰难细菌均未显示出完全杀菌活性，表明具有种属和核糖体型特异性。功能基因，这可能是必要的杀伤，被确定在PTLP的遗传locus.ConclusionPTLPs证明根除艰难梭菌在体外的能力，并与进一步发展，可能代表一个有机体特异性，微生物保留治疗CDI。
BackgroundCurrentClostridium difficileinfection (CDI) antibiotic regimens have become increasingly ineffective at achieving cure and preventing recurrence. A recently developed alternative to conventional antibiotics are phage tail-like particles (PTLPs), which are proteins that are morphologically similar to bacteriophages and are produced byC difficile. This study examines the in vitro killing spectrum of a previously unreported PTLP isolated from a clinical isolate ofC difficile.MethodsUsing patient-derived samples from an institutional review board-approvedC difficiletissue bank, a ribotype 078C difficileisolate was anaerobically incubated on blood agar plates that were preswabbed with norfloxacin to induce the production of PTLPs. Concentrated PTLP populations were confirmed using transmission electron microscopy. Using a standard lawn spot approach, bactericidal activity was assessed as indicated by a clearing within the bacterial lawn. The PTLP genomic cluster was also fully sequenced and open reading frames were annotated according to predicted function.ResultsPTLPs were assessed using 64 patient-derivedC difficileisolates of varying ribotypes. PTLPs demonstrated complete bactericidal activity in 21 of 25 ribotype 027 isolates with partial activity in 2 of the 25. Complete bactericidal activity was not demonstrated against any other ribotype or non-difficilebacteria, suggesting a species and ribotype specificity. Functional genes, which may be necessary for killing, were identified within the PTLP genetic locus.ConclusionPTLPs demonstrate capability in eradicatingC difficilein vitro, and with further development, may represent an organism-specific, microbiome-sparing therapy for CDI.
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