Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland.
Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.
Curr Opin Biotechnol. 2021 Apr;68:272-281. doi: 10.1016/j.copbio.2021.02.006. Epub 2021 Mar 18.
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.
噬菌体（phages）在感染过程中使用专门的尾部机制将蛋白质和遗传物质递送到细菌细胞内。它们的尾部末端附着有受体结合蛋白（RBPs），能够识别宿主细菌表面暴露的特定分子。由于天然噬菌体的治疗能力常常受到宿主范围狭窄的限制，因此通过定向进化或对其 RBPs 进行结构导向工程来扩大其宿主范围具有重要意义。在这里，我们描述了不同 RBP 工程平台的设计原则，并提请注意将 RBP 结合与噬菌体正确地在空间和时间上附着到细菌表面的机制联系起来。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。
