Biomedical Engineering Department, Boston University, Boston, MA 02215.
Biological Design Center, Boston University, Boston, MA 02215.
Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2115032119. doi: 10.1073/pnas.2115032119. Epub 2022 Mar 28.
Cell-to-cell heterogeneity in gene expression and growth can have critical functional consequences, such as determining whether individual bacteria survive or die following stress. Although phenotypic variability is well documented, the dynamics that underlie it are often unknown. This information is important because dramatically different outcomes can arise from gradual versus rapid changes in expression and growth. Using single-cell time-lapse microscopy, we measured the temporal expression of a suite of stress-response reporters in Escherichia coli, while simultaneously monitoring growth rate. In conditions without stress, we found several examples of pulsatile expression. Single-cell growth rates were often anticorrelated with reporter levels, with changes in growth preceding changes in expression. These dynamics have functional consequences, which we demonstrate by measuring survival after challenging cells with the antibiotic ciprofloxacin. Our results suggest that fluctuations in both gene expression and growth dynamics in stress-response networks have direct consequences on survival.
细胞间基因表达和生长的异质性可能具有关键的功能后果，例如决定单个细菌在压力后是存活还是死亡。尽管表型变异性有充分的记录，但支持它的动力学通常是未知的。这一信息很重要，因为表达和生长的逐渐变化与快速变化可能会产生截然不同的结果。我们使用单细胞延时显微镜，在同时监测生长速率的情况下，测量了一系列应激反应报告基因在大肠杆菌中的时间表达。在没有压力的条件下，我们发现了几个脉冲表达的例子。单细胞生长速率通常与报告基因水平呈负相关，生长的变化先于表达的变化。这些动态具有功能后果，我们通过测量用抗生素环丙沙星挑战细胞后的存活率来证明这一点。我们的结果表明，应激反应网络中基因表达和生长动力学的波动对生存有直接影响。
