Cesar Spencer, Willis Lisa, Huang Kerwyn Casey
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
iScience. 2022 Jan 15;25(3):103765. doi: 10.1016/j.isci.2022.103765. eCollection 2022 Mar 18.
Bacterial survival is often challenged by nutrient-depleted conditions. Here, we show that regrowth from prolonged stationary phase is heterogeneous. Some cells rejuvenated immediately, even after extended starvation, but others only restarted growth after a delay or not at all. The proportion of nongrowing cells increased with time spent in stationary phase, rather than time-dependent medium changes. Delayed regrowth was correlated with the dissolution of polar phase-bright foci likely representing damaged protein aggregates, and a deep learning algorithm distinguished cellular fates based on single images. Delayed regrowth initiated after upregulation of chaperones and DNA-repair enzymes, and deletion of a chaperone compromised stationary-phase morphology and increased the nongrowing cell proportion. Mathematical modeling of damage accumulation and division-mediated partitioning quantitatively predicted all rejuvenation statistics. Cells regrew immediately after starving in the absence of respiration. These findings reinforce the importance of intracellular damage control when nutrients are sparse, and repair when nutrients are plentiful.
细菌的生存常常受到营养匮乏条件的挑战。在此，我们表明，长时间稳定期后的再生长是异质性的。一些细胞即使在长期饥饿后也能立即恢复活力，但另一些细胞则会延迟生长或根本不再生长。不生长细胞的比例随在稳定期所花费的时间增加，而非随时间依赖性的培养基变化而增加。延迟再生长与可能代表受损蛋白质聚集体的极性相亮斑的溶解相关，并且一种深度学习算法基于单张图像区分细胞命运。延迟再生长在伴侣蛋白和DNA修复酶上调后开始，并且删除一种伴侣蛋白会损害稳定期形态并增加不生长细胞的比例。损伤积累和分裂介导的分配的数学模型定量预测了所有恢复活力的统计数据。在无呼吸条件下饥饿后细胞立即再生长。这些发现强化了营养稀缺时细胞内损伤控制以及营养充足时修复的重要性。
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