Bruckbauer Steven T, Martin Joel, Minkoff Benjamin B, Veling Mike T, Lancaster Illissa, Liu Jessica, Trimarco Joseph D, Bushnell Brian, Lipzen Anna, Wood Elizabeth A, Sussman Michael R, Pennacchio Christa, Cox Michael M
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, United States.
DOE Joint Genome Institute, Berkeley, CA, United States.
Front Microbiol. 2020 Sep 22;11:582590. doi: 10.3389/fmicb.2020.582590. eCollection 2020.
Ionizing radiation (IR) is lethal to most organisms at high doses, damaging every cellular macromolecule via induction of reactive oxygen species (ROS). Utilizing experimental evolution and continuing previous work, we have generated the most IR-resistant populations developed to date. After 100 cycles of selection, the dose required to kill 99% the four replicate populations (IR9-100, IR10-100, IR11-100, and IR12-100) has increased from 750 Gy to approximately 3,000 Gy. Fitness trade-offs, specialization, and clonal interference are evident. Long-lived competing sub-populations are present in three of the four lineages. In IR9, one lineage accumulates the heme precursor, porphyrin, leading to generation of yellow-brown colonies. Major genomic alterations are present. IR9 and IR10 exhibit major deletions and/or duplications proximal to the chromosome replication terminus. Contributions to IR resistance have expanded beyond the alterations in DNA repair systems documented previously. Variants of proteins involved in ATP synthesis (AtpA), iron-sulfur cluster biogenesis (SufD) and cadaverine synthesis (CadA) each contribute to IR resistance in IR9-100. Major genomic and physiological changes are emerging. An isolate from IR10 exhibits protein protection from ROS similar to the extremely radiation resistant bacterium , without evident changes in cellular metal homeostasis. Selection is continuing with no limit to IR resistance in evidence as our populations approach levels of IR resistance typical of .
高剂量的电离辐射（IR）对大多数生物体都是致命的，它通过诱导活性氧（ROS）破坏每个细胞大分子。利用实验进化并延续之前的工作，我们培育出了迄今为止最抗IR的群体。经过100代选择后，杀死四个重复群体（IR9 - 100、IR10 - 100、IR11 - 100和IR12 - 100）中99%个体所需的剂量已从750戈瑞增加到约3000戈瑞。适应性权衡、特化和克隆干扰很明显。四个谱系中的三个存在长寿的竞争亚群体。在IR9中，一个谱系积累血红素前体卟啉，导致产生黄棕色菌落。存在主要的基因组改变。IR9和IR10在染色体复制终点附近表现出主要的缺失和/或重复。对IR抗性的贡献已超出先前记录的DNA修复系统改变的范围。参与ATP合成（AtpA）、铁硫簇生物合成（SufD）和尸胺合成（CadA）的蛋白质变体各自对IR9 - 100中的IR抗性有贡献。主要的基因组和生理变化正在显现。从IR10分离出的一个菌株表现出类似于极端抗辐射细菌的对ROS的蛋白质保护，而细胞金属稳态没有明显变化。选择仍在继续，随着我们的群体接近典型的IR抗性水平，IR抗性没有明显的极限。
