From protein damage to cell aging to population fitness in E. coli: Insights from a multi-level agent-based model

Aging is an important process affecting many organisms, including bacteria that appear to divide symmetrically. Recent research has established much of the mechanisms underlying aging in Escherichia coli, including the role of damaged protein aggregates (DPAs) that are transported by diffusion within the nucleoid-free intracellular space, which leads to their polar localization and asymmetric inheritance (i.e. aging). This provides an opportunity to develop a mechanistic model of E. coli and use it to assess the role of this process at the population level. Is there a fitness benefit to asymmetric inheritance of DPAs? Here we explore this question using a multi-level agent-based model, which simulates a population of individual cells, each with a population of individual DPAs. The model is compared to relevant data compiled from four published studies, which shows it reproduces the main patterns observed, including intracellular localization and inheritance of DPAs, their effect on growth rate, differences in growth rate between sibling pairs, under unstressed and heat shock conditions, for wild type and a mutant that partitions DPAs symmetrically. The model is used to estimate population growth rates of the wildtype and mutant, which shows a statistically significant benefit of aging by asymmetric DPA segregation. However, the benefit is very small and probably not relevant in the context of the ecology of the bacteria's primary habitat (the intestinal tract of warm-blooded animals). But, at an evolutionary time scale even this small benefit may be relevant for bacteria with large population sizes and short generation times.