Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Winnipeg, Manitoba R3T 2N2, Canada.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543 - 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada.
FEMS Microbiol Rev. 2022 May 6;46(3). doi: 10.1093/femsre/fuac005.
Essential genes encode the processes that are necessary for life. Until recently, commonly applied binary classifications left no space between essential and non-essential genes. In this review, we frame bacterial gene essentiality in the context of genetic networks. We explore how the quantitative properties of gene essentiality are influenced by the nature of the encoded process, environmental conditions and genetic background, including a strain's distinct evolutionary history. The covered topics have important consequences for antibacterials, which inhibit essential processes. We argue that the quantitative properties of essentiality can thus be used to prioritize antibacterial cellular targets and desired spectrum of activity in specific infection settings. We summarize our points with a case study on the core essential genome of the cystic fibrosis pathobiome and highlight avenues for targeted antibacterial development.
必需基因编码的过程是生命所必需的。直到最近,常用的二进制分类方法在必需基因和非必需基因之间没有留下任何空间。在这篇综述中,我们将细菌基因的必需性置于遗传网络的背景下进行研究。我们探讨了基因必需性的定量特性如何受到所编码过程的性质、环境条件和遗传背景的影响,包括菌株独特的进化历史。所涵盖的主题对抗菌药物有重要的影响,因为它们抑制了必需的过程。我们认为,必需性的定量特性可以用于确定抗菌药物的细胞靶标和在特定感染环境中的所需作用谱。我们用囊性纤维化病理生物群的核心必需基因组的案例研究来总结我们的观点,并强调了靶向抗菌药物开发的途径。