Boehm Alex, Arnoldini Markus, Bergmiller Tobias, Röösli Thomas, Bigosch Colette, Ackermann Martin
Biozentrum, University of Basel, Switzerland.
Philipps-Universität Marburg, LOEWE-Zentrum für Synthetische Mikrobiologie, Marburg, Germany.
PLoS Genet. 2016 Apr 19;12(4):e1005974. doi: 10.1371/journal.pgen.1005974. eCollection 2016 Apr.
In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported.
在细菌中,复制性衰老表现为细胞分裂产生的两个子代细胞在生长或存活方面的差异。一个细胞可被视为衰老的母细胞,其未来存活和分裂的潜力降低,另一个则是恢复活力的子代细胞。在此,我们旨在研究大肠杆菌衰老过程中涉及的一些机制,在这种细菌中,这两种细胞类型可通过其细胞极的年龄来区分。我们发现碳水化合物代谢调控的某些变化会影响衰老。碳储存调节基因csrA发生突变会导致复制寿命显著缩短;csrA突变体一旦其细胞极超过约五个分裂周期的年龄就会停止分裂。这些具有老细胞极的细胞在其老细胞极积累糖原;在它们最后一次分裂后,它们不含染色体,推测是由于糖原聚集体的空间排斥作用。这些衰老母细胞产生的新极子代细胞出生时是年轻的;只有当它们的细胞极变老时才会表现出有害表型。这些结果表明营养分配的调控如何导致染色体被排斥并限制大肠杆菌的复制寿命,并说明了突变如何产生对具有老细胞极的细胞具有特异性的表型效应。这就提出了一个问题,即细菌如何在进化过程中避免其基因组中积累此类突变,以及它们如何实现最近报道的长复制寿命。