Dynamic structure of E. coli cytoplasm: supramolecular complexes and cell aging impact spatial distribution and mobility of proteins

Aging, the decline in physiological function over time, is marked by the intracellular accumulation of damaged components. It can be attributed to a trade-off between the investment into organismal maintenance and the production of high-quality offspring, where the parent accumulates damage over time and retains it upon reproduction, while the offspring is rejuvenated. Asymmetric damage partitioning has been observed even in simple unicellular organisms, such as Escherichia coli cells that retain aggregates of misfolded proteins during cell division. However, recent studies presented conflicting evidence on the effect of protein aggregates on fitness, ranging from detrimental effects on cell growth to enhanced stress survival. Here, we show that the decisive factor driving growth decline in E. coli is not the presence of a protein aggregate, but the proportion of the intracellular space occupied by it. By following single-cell E. coli lineages expressing fluorescently labeled DnaK chaperones, we quantified damage accumulation and partitioning across generations in microfluidic devices. Our results suggest that the aggregation of damaged proteins allows cells to keep damage separate from vital processes and compensate for the lost intracellular space by growing to larger sizes, a process which results in morphologically asymmetrical divisions. In line with other recent evidence, this points to a more complex role of protein aggregation, with implications for our understanding of the cellular mechanisms underlying aging as well as its evolutionary origins.

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Progressive decline in old pole gene expression signal enhances phenotypic heterogeneity in bacteria

Proenca,

Tuğrul,

Nath

et al. 2024

Sci. Adv.

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Cell growth and gene expression are heterogeneous processes at the single-cell level, leading to the emergence of multiple physiological states within bacterial populations. Aging is a known deterministic driver of growth asymmetry; however, its role in gene expression heterogeneity remains elusive. Here, we show that aging mother cells undergo a progressive decline in old pole activity, generating asymmetry in protein partitioning, gene expression, and cell morphology. We demonstrate that mother cells, when compared to their daughters, exhibit lower product inheritance and gene expression rates independently of promoter dynamics. The declining activity of maternal old poles generates gene expression gradients that manifest as mother-daughter asymmetry upon division, showing that asymmetry is progressively built over time within the maternal intracellular environment. Moreover, old pole aging correlates with a gradual increase in cell length, leading to morphological asymmetry. These findings provide further evidence for aging as a mechanism to enhance phenotypic heterogeneity in bacterial populations, with possible consequences for stress response and survival.

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Dynamic structure of E. coli cytoplasm: supramolecular complexes and cell aging impact spatial distribution and mobility of proteins

Cited by 3 publications

References 48 publications

Role of protein aggregates in bacteria

Role of protein aggregates in bacteria

Protein aggregation drives cell aging in a size-specific manner inEscherichia coli

Progressive decline in old pole gene expression signal enhances phenotypic heterogeneity in bacteria

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