320 Longwood Avenue, Enders Building, Department of Infectious Disease, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.
J Med Microbiol. 2020 Feb;69(2):309-323. doi: 10.1099/jmm.0.001162. Epub 2020 Feb 3.
Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established. Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative (EAEC) while leaving the human microbiome intact. Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage, , was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment. virus , a member of the strictly lytic family , killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of (multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces. also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and , or with just phage was not different statistically. killed EAEC isolate EN1E-0007 and , while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller's diarrhoea without causing dysbiosis.
噬菌体疗法可以针对新发的腹泻病原体进行开发,但在不破坏微生物组的情况下这样做尚未得到证实,抗生素治疗会导致微生物组破坏。确定一种能够杀死致腹泻性聚集性大肠杆菌(EAEC)而不破坏人类微生物组的治疗性噬菌体。通过覆盖测定筛选来自美国俄勒冈州波特兰市废水的噬菌体以确定其裂解活性。分离到的一种噬菌体, ,通过电子显微镜和基因组测序进行分类。通过感染小鼠模型确定该噬菌体是否对 EAEC 具有治疗作用。通过厌氧培养的 16S 宏基因组分析确定治疗是否改变了正常的人类微生物组。 病毒,一种严格的裂解家族成员,以剂量依赖性方式杀死了来自田纳西州农村的一名儿童的与病例相关的 EAEC 分离株,并且还杀死了哥伦比亚儿童的 EAEC 分离株。感染后 1 天给予单剂量 (感染复数:100)可减少从小鼠粪便中回收的 EAEC。在存在人粪便细菌的情况下进行厌氧培养时, 也可以杀死 EAEC。虽然 EAEC 的添加降低了人类微生物组的 β 多样性,但仅添加粪便、添加 EAEC 和 、或仅添加 噬菌体的培养物的 β 多样性在统计学上没有差异。 杀死了 EAEC 分离株 EN1E-0007 和 ,而在厌氧培养中不改变正常人类微生物组的多样性,因此可以成为发展中国家儿童和遭受 EAEC 介导的旅行者腹泻的患者的有效治疗方法,而不会导致菌群失调。