Reprogramming bacteriophage host range: design principles and strategies for engineering receptor binding proteins.

Reprogramming bacteriophage host range: design principles and strategies for engineering receptor binding proteins.
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DOI:
10.1016/j.copbio.2021.02.006
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发表时间:
2021-04
影响因子:
7.7
通讯作者:
--
中科院分区:
工程技术1区
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--
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噬菌体(Bacteriophage,缩写为Bacteriophage)在感染过程中使用专门的尾部机制将蛋白质和遗传物质输送到细菌细胞中。在它们尾部的末端附着的是受体结合蛋白(RBP),它识别暴露在宿主细菌表面的特定分子。由于天然存在的RBP的治疗能力通常受到狭窄宿主范围的限制,因此通过其RBP的定向进化或结构引导工程来扩大其宿主范围具有重大意义。在这里,我们描述了不同的RBP工程平台的设计原则,并提请注意连接RBP结合和正确的空间和时间的连接噬菌体的细菌表面的机制。对这些机制的更深入理解将直接有益于未来更有效的基于噬菌体的治疗方法的工程设计。
Bacteriophages (phages) use specialized tail machinery to deliver proteins and genetic material into a bacterial cell during infection. Attached at the distal ends of their tails are receptor binding proteins (RBPs) that recognize specific molecules exposed on host bacteria surfaces. Since the therapeutic capacity of naturally occurring phages is often limited by narrow host ranges, there is significant interest in expanding their host range via directed evolution or structure-guided engineering of their RBPs. Here, we describe the design principles of different RBP engineering platforms and draw attention to the mechanisms linking RBP binding and the correct spatial and temporal attachment of the phage to the bacterial surface. A deeper understanding of these mechanisms will directly benefit future engineering of more effective phage-based therapeutics.
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