T4 phages against Escherichia coli diarrhea: Potential and problems
T4 phages against Escherichia coli diarrhea: Potential and problems
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DOI：
10.1016/j.virol.2009.03.009
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发表时间：
2009-05-25
期刊：
影响因子：
3.7
通讯作者：
Zuber, Sophie
中科院分区：
文献类型：
--
作者：
Denou, Emmanuel;Bruttin, Anne;Zuber, Sophie
结合体内外实验和比较噬菌体基因组学，合理设计了抗大肠杆菌的噬菌体混合物。大肠杆菌腹泻。代表三个不同亚组（T4-、RB 49-和JS 98-样大肠杆菌）的口服施用的T4大肠杆菌对鼠肠道微生物群没有负面影响。在盲肠和结肠中发现了高滴度的T4 β，在小肠中发现了较低滴度，但在血液、肝脏或脾脏中未检测到。暴露于噬菌体一个月后未观察到不良反应，也未检测到血清抗T4抗体。属于同一亚组的T4噬菌体显示出密切相关的基因组，其差异为12（噬菌体JS 10相对于JS 98参考）至17（噬菌体JSE相对于RB 49参考）插入/缺失，主要代表单个小ORF。生物信息学分析没有揭示T4基因组中的不期望的基因。序列变异性被认为是在尾纤维基因，但变异性与噬菌体宿主范围不相关。所研究的T4噬菌体不仅是种特异性的，而且是菌株特异性的，需要使用由10个和16个T4噬菌体分离物组成的噬菌体混合物来覆盖一半至三分之二的E.大肠杆菌菌株代表了从腹泻患者中分离的5种主要致病型。(C)2009 Elsevier Inc.版权所有
A combination of in vitro and in vivo experiments with comparative phage genomics was Used for the rational design of a phage cocktail against E. coli diarrhea. Orally applied T4 coliphages representing three different Subgroups (T4-, RB49- and JS98-like phages) had no negative impact on the murine got microbiota. T4 phages were found with high titers in the cecum and colon and lower titers in the small intestine but, were not detected in the blood, liver or spleen. No adverse effects were observed after one-month exposure to phage nor were serum anti-T4 antibodies detected. T4 phages belonging to the same Subgroup showed closely related genomes that differed by 12 (phage JS10 vs. JS98 reference) to 17 (phage JSE vs. RB49 reference) insertion/deletions mostly representing single small ORFs. Bioinformatic analysis did not reveal undesired genes in the T4 genomes. Sequence variability was seen over the tail fibre genes, but the variability did not correlate with phage host range. The investigated T4 phages were not only species- but also strain-specific, necessitating the use of phage cocktails consisting of 10 and 16 T4 phage isolates to cover half to two thirds of E. coli strains representing the five main pathotypes isolated from diarrhea patients. (C) 2009 Elsevier Inc. All rights reserved