噬菌体疗法
生物
基因组
合成生物学
细菌
噬菌体
抗生素耐药性
转化(遗传学)
计算生物学
抗生素
遗传学
微生物学
基因
大肠杆菌
作者
Jonas Fernbach,Susanne Meile,Samuel Kilcher,Martin J. Loessner
出处
期刊:Methods in molecular biology
日期:2023-12-09
卷期号:: 247-259
被引量:2
标识
DOI:10.1007/978-1-0716-3523-0_16
摘要
The rapid increase of circulating, antibiotic-resistant pathogens is a major ongoing global health crisis, and arguably, the end of the "golden age of antibiotics" is looming. This has led to a surge in research and development of alternative antimicrobials, including bacteriophages, to treat such infections (phage therapy). Isolating natural phage variants for the treatment of individual patients is an arduous and time-consuming task. Furthermore, the use of natural phages is frequently hampered by natural limitations, such as moderate in vivo activity, the rapid emergence of resistance, insufficient host range, or the presence of undesirable genetic elements within the phage genome. Targeted genetic editing of wild-type phages (phage engineering) has successfully been employed in the past to mitigate some of these pitfalls and to increase the therapeutic efficacy of the underlying phage variants. Clearly, there is a large potential for the development of novel, marker-less genome-editing methodologies to facilitate the engineering of therapeutic phages. Steady advances in synthetic biology have facilitated the in vitro assembly of modified phage genomes, which can be activated ("rebooted") upon transformation of a suitable host cell. However, this can prove challenging, especially in difficult-to-transform Gram-positive bacteria. In this chapter, we detail the productionProduction of cell wall-deficient L-form bacteria and their application to activate synthetic genomes of phages infecting Gram-positive host species.
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