Jia Huang-Jie, Jia Pan-Pan, Yin Supei, Bu Ling-Kang, Yang Guan, Pei De-Sheng
College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China.
Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China.
Front Microbiol. 2023 May 31;14:1172635. doi: 10.3389/fmicb.2023.1172635. eCollection 2023.
Bacteriophages, the most abundant organisms on earth, have the potential to address the rise of multidrug-resistant bacteria resulting from the overuse of antibiotics. However, their high specificity and limited host range can hinder their effectiveness. Phage engineering, through the use of gene editing techniques, offers a means to enhance the host range of bacteria, improve phage efficacy, and facilitate efficient cell-free production of phage drugs. To engineer phages effectively, it is necessary to understand the interaction between phages and host bacteria. Understanding the interaction between the receptor recognition protein of bacteriophages and host receptors can serve as a valuable guide for modifying or replacing these proteins, thereby altering the receptor range of the bacteriophage. Research and development focused on the CRISPR-Cas bacterial immune system against bacteriophage nucleic acids can provide the necessary tools to promote recombination and counter-selection in engineered bacteriophage programs. Additionally, studying the transcription and assembly functions of bacteriophages in host bacteria can facilitate the engineered assembly of bacteriophage genomes in non-host environments. This review highlights a comprehensive summary of phage engineering methods, including in-host and out-of-host engineering, and the use of high-throughput methods to understand their role. The main aim of these techniques is to harness the intricate interactions between bacteriophages and hosts to inform and guide the engineering of bacteriophages, particularly in the context of studying and manipulating the host range of bacteriophages. By employing advanced high-throughput methods to identify specific bacteriophage receptor recognition genes, and subsequently introducing modifications or performing gene swapping through in-host recombination or out-of-host synthesis, it becomes possible to strategically alter the host range of bacteriophages. This capability holds immense significance for leveraging bacteriophages as a promising therapeutic approach against antibiotic-resistant bacteria.
噬菌体是地球上数量最多的生物体，有潜力应对因抗生素过度使用导致的多重耐药细菌的增加。然而，它们的高特异性和有限的宿主范围可能会阻碍其有效性。通过使用基因编辑技术进行噬菌体工程，提供了一种扩大噬菌体宿主范围、提高噬菌体疗效以及促进噬菌体药物高效无细胞生产的方法。为了有效地改造噬菌体，有必要了解噬菌体与宿主细菌之间的相互作用。了解噬菌体的受体识别蛋白与宿主受体之间的相互作用，可以为修饰或替换这些蛋白提供有价值的指导，从而改变噬菌体的受体范围。针对噬菌体核酸的CRISPR-Cas细菌免疫系统的研发，可以提供必要的工具来促进工程噬菌体程序中的重组和反选择。此外，研究噬菌体在宿主细菌中的转录和组装功能，可以促进噬菌体基因组在非宿主环境中的工程组装。本综述全面总结了噬菌体工程方法，包括宿主内和宿主外工程，以及使用高通量方法来了解它们的作用。这些技术的主要目的是利用噬菌体与宿主之间复杂的相互作用，为噬菌体工程提供信息和指导，特别是在研究和操纵噬菌体宿主范围的背景下。通过采用先进的高通量方法来鉴定特定的噬菌体受体识别基因，随后通过宿主内重组或宿主外合成进行修饰或基因交换，有可能策略性地改变噬菌体的宿主范围。这种能力对于将噬菌体作为对抗抗生素耐药细菌的一种有前途的治疗方法具有巨大意义。
