School of Pharmacy, University of Waterloo, Ontario N2L 3G1, Canada.
School of Pharmacy, University of Waterloo, Ontario N2L 3G1, Canada
Genetics. 2020 Dec;216(4):1087-1102. doi: 10.1534/genetics.120.303643. Epub 2020 Oct 8.
The T4r exclusion (Rex) phenotype is the inability of T4 mutant bacteriophage to propagate in hosts () lysogenized by bacteriophage lambda (λ). The Rex phenotype, triggered by T4 infection of a λ lysogen, results in rapid membrane depolarization imposing a harsh cellular environment that resembles stationary phase. Rex "activation" has been proposed as an altruistic cell death system to protect the λ prophage and its host from T4r superinfection. Although well studied for over 60 years, the mechanism behind Rex still remains unclear. We have identified key nonessential genes involved in this enigmatic exclusion system by examining T4r infection across a collection of single-gene knockouts. We further developed a system for rapid, one-step isolation of host mutations that could attenuate/abrogate the Rex phenotype. For the first time, we identified host mutations that influence Rex activity and host sensitivity to T4 infection. Among others, notable genes include , , , , , , , , and They are critical players in cellular osmotic balance and are part of the stationary phase and/or membrane distress regulons. Based on these findings, we propose a new model that connects Rex to the σ, σ regulons and key membrane proteins.
T4r 排除（Rex）表型是指 T4 突变噬菌体在被噬菌体 λ（λ）溶源化的宿主中无法繁殖的能力。Rex 表型是由 T4 感染 λ 溶源体引发的，导致快速的膜去极化，从而产生类似于静止期的苛刻细胞环境。Rex“激活”被提议为一种利他的细胞死亡系统，以保护 λ 前噬菌体及其宿主免受 T4r 的超感染。尽管 Rex 已经被研究了 60 多年，但它背后的机制仍然不清楚。我们通过检查跨越一系列单基因敲除体的 T4r 感染，鉴定了参与这个神秘排除系统的关键非必需基因。我们进一步开发了一种快速、一步分离宿主突变的系统，这些突变可以减弱/消除 Rex 表型。我们首次鉴定了影响 Rex 活性和宿主对 T4 感染敏感性的宿主突变。其中包括、、、、、、、和。它们是细胞渗透平衡的关键参与者，是静止期和/或膜应激调节子的一部分。基于这些发现，我们提出了一个新的模型，将 Rex 与 σ、σ 调节子和关键膜蛋白联系起来。
