中文摘要：噬菌体是一种感染细菌的病毒，由于其无与伦比的多样性及最近在基因工程方面的突破，在治疗耐多药细菌感染和其他应用方面潜力巨大。然而，噬菌体-宿主相互作用的分子机制的基础知识大多局限于少数传统的模型系统，不能跟上该领域最近的快速发展。因此，由这些病毒编码的分子生物学的真正潜力在很大程度上尚未开发，用于治疗或其他应用的噬菌体通常仍需根据经验选择。为此，本研究构建了一个由68个新近分离并感染模式生物大肠杆菌的噬菌体库，作为BASEL（实验室噬菌体选择）共享库，来系统性探索噬菌体-宿主相互作用。该库在很大程度上代表了天然大肠杆菌噬菌体的多样性，并与10个已充分研究的传统模型噬菌体一起进行了表型和基因组特征分析。实验确定了所有噬菌体的主要宿主受体，量化了它们对细菌免疫不同层次的11种防御系统的敏感性，并将这些结果与噬菌体在一组致病性肠道细菌菌株中的宿主范围相匹配。噬菌体表型和基因组特征分布的清晰模式突出了不同免疫系统效力的系统差异，并提示了几个噬菌体群体中受体特异性的分子基础。研究还表明，适应性特征（如广泛的宿主识别）和细菌免疫抵抗力（可能导致不同噬菌体群对特定生态位的不同适应）之间存在着强烈的平衡。可以预见，BASEL库将通过促进潜在分子机制的发现作为有效转化为生物技术或治疗应用的基础，激发未来探索噬菌体及其宿主生物学的工作。
外文摘要：Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage-host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage-host interactions by composing a well-assorted library of 68 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL (BActeriophage SElection for your Laboratory) collection. This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside 10 well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to 11 defense systems across different layers of bacterial immunity, and matched these results to the phages' host range across a panel of pathogenic enterobacterial strains. Clear patterns in the distribution of phage phenotypes and genomic features highlighted systematic differences in the potency of different immunity systems and suggested the molecular basis of receptor specificity in several phage groups. Our results also indicate strong trade-offs between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific ecological niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.
外文关键词：RESTRICTION-MODIFICATION ENZYMES；B STRAINS REL606；BACTERIOPHAGE-LAMBDA；RECEPTOR-BINDING；GENOME SEQUENCES；BACTERIAL； PROTEIN；GENES；TAXONOMY；MECHANISMS
作者：Maffei, E；Shaidullina, A；Burkolter, M；Heyer, Y；Estermann, F；Druelle, V；Sauer, P；Willi, L；Michaelis, S；Hilbi, H；Thaler, DS；Harms, A
作者单位：Univ Basel；Univ Zurich；Rockefeller Univ
期刊名称：PLOS BIOLOGY
期刊影响因子：7.076
出版年份：2021
出版刊次：11
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