中文摘要：Ackermannviridae家族噬菌体编码的尾刺蛋白（TSPs）多达四种，每种都识别其细菌宿主的特定受体。本文通过进行全面的信息学分析确定99个Ackermannviridae噬菌体的TSPs多样性。基于序列多样性，将所有TSP分为4个亚型：TSP1、TSP2、TSP3和TSP4，并且每个亚型都与Ackermannviridae家族的属（Kuttervirus、Agtrevirus、Limestonevirus、Taipeivirus）特异相关。进一步分析发现，TSP2和TSP4中连接四个TSPs的N-末端XD1和XD2结构域得以保留。相反，C-末端受体结合模块，除了一些类似于特定TSP4的Kuttervirus TSP1s和TSP3外，仅在TSP亚型中保留。Kuttervirus噬菌体的TSP1、TSP3和TSP4中的保守基序允许受体结合模块之间的重组，从而改变宿主识别。使用先前的宿主范围数据预测了表达相同TSP亚型的众多未鉴定噬菌体的受体，并通过实验确定了kuttervirus 5117表达的四种TSP中的三种的宿主识别，验证了这些预测；证实了5117的TSP1和TSP2与预测的宿主受体结合，并鉴定了TSP3的受体，该受体被51个其他Kuttervirus噬菌体共享。由此，Kuttervirus噬菌体显示了影响宿主识别的潜在可交换TSP的巨大遗传多样性。可见，对TSP进行全面的信息学和宿主范围分析可以预测Ackermannviridae噬菌体的宿主识别。
外文摘要：Phages belonging to the Ackermannviridae family encode up to four tail spike proteins (TSPs), each recognizing a specific receptor of their bacterial hosts. Here, we determined the TSPs diversity of 99 Ackermannviridae phages by performing a comprehensive in silico analysis. Based on sequence diversity, we assigned all TSPs into distinctive subtypes of TSP1, TSP2, TSP3 and TSP4, and found each TSP subtype to be specifically associated with the genera (Kuttervirus, Agtrevirus, Limestonevirus, Taipeivirus) of the Ackermannviridae family. Further analysis showed that the N-terminal XD1 and XD2 domains in TSP2 and TSP4, hinging the four TSPs together, are preserved. In contrast, the C-terminal receptor binding modules were only conserved within TSP subtypes, except for some Kuttervirus TSP1 s and TSP3s that were similar to specific TSP4s. A conserved motif in TSP1, TSP3 and TSP4 of Kuttervirus phages may allow recombination between receptor binding modules, thus altering host recognition. The receptors for numerous uncharacterized phages expressing TSPs in the same subtypes were predicted using previous host range data. To validate our predictions, we experimentally determined the host recognition of three of the four TSPs expressed by kuttervirus 5117. We confirmed that 5117 TSP1 and TSP2 bind to their predicted host receptors, and identified the receptor for TSP3, which is shared by 51 other Kuttervirus phages. Kuttervirus phages were thus shown encode a vast genetic diversity of potentially exchangeable TSPs influencing host recognition. Overall, our study demonstrates that comprehensive in silico and host range analysis of TSPs can predict host recognition of Ackermannviridae phages.
外文关键词：Bacteriophage；Ackermannviridae family；Receptor-binding proteins；Tail spike proteins；Host range；O-antigen；Escherichia coli O:157；Salmonella
作者：Sorensen, AN；Woudstra, C；Sorensen, MCH；Brondsted, L
作者单位：Univ Copenhagen
期刊名称：COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
期刊影响因子：6.018
出版年份：2021
出版刊次：19
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