PDF(Pubmed)
Abstract：
Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms\' long-term adaptation to new environments. However, loss-of-function mutations are often deleterious, triggering, in turn, cellular stress and complex homeostatic stress responses, called \"allostasis,\" to promote cell survival. Here, we characterize the differential impacts of 65 nonlethal, deleterious single-gene deletions on Escherichia coli growth in three different growth environments. Further assessments of select mutants, namely, those bearing single adenosine triphosphate (ATP) synthase subunit deletions, reveal that mutants display reorganized transcriptome profiles that reflect both the environment and the specific gene deletion. We also find that ATP synthase α-subunit deleted (ΔatpA) cells exhibit elevated metabolic rates while having slower growth compared to wild-type (wt) E. coli cells. At the single-cell level, compared to wt cells, individual ΔatpA cells display near normal proliferation profiles but enter a postreplicative state earlier and exhibit a distinct senescence phenotype. These results highlight the complex interplay between genomic diversity, adaptation, and stress response and uncover an \"aging cost\" to individual bacterial cells for maintaining population-level resilience to environmental and genetic stress; they also suggest potential bacteriostatic antibiotic targets and -as select human genetic diseases display highly similar phenotypes, - a bacterial origin of some human diseases.
摘要：
随机诱变,包括当它导致基因功能丧失时，是使微生物能够长期适应新环境的关键机制。然而,功能丧失突变通常是有害的，触发,反过来,细胞应激和复杂的稳态应激反应，叫做“同种异体，“促进细胞存活。这里,我们描述了65种非致命性，在三种不同的生长环境中，对大肠杆菌生长的有害单基因缺失。对选定突变体的进一步评估，即,那些带有单个三磷酸腺苷（ATP）合酶亚基缺失的人，揭示突变体显示重组的转录组谱，反映了环境和特定基因的缺失。我们还发现，与野生型（wt）大肠杆菌细胞相比，ATP合酶α亚基缺失（ΔatpA）细胞的代谢率升高，而生长较慢。在单细胞层面,与wt细胞相比，单个ΔatpA细胞显示接近正常的增殖曲线，但较早进入复制后状态并表现出明显的衰老表型。这些结果突出了基因组多样性之间复杂的相互作用，适应,和应激反应，并揭示了一个“老化成本”的个体细菌细胞，以维持群体水平的环境和遗传胁迫的恢复力;他们还提出了潜在的抑菌抗生素靶标，并且-由于某些人类遗传疾病表现出高度相似的表型，-一些人类疾病的细菌起源。
