Bet-hedging and epigenetic inheritance in bacterial cell development

TLDR

Upon nutritional limitation, Bacillus subtilis can irreversibly sporulate, a bistable process in which only a subpopulation becomes endospores, yet the determinants of this decision remain poorly understood. Using time‑lapse microscopy, we tracked individual cells to identify historical and ancestral factors that influence sporulation decisions. We found that B. subtilis employs a bet‑hedging strategy—some cells sporulate while others continue growth on alternative metabolites, giving the latter a reproductive advantage; aging does not affect fate, but the physiological state of an ancestor more than two generations earlier influences differentiation through positive feedback in the sporulation phosphorelay, creating an intergenerational memory that may support multicellular structures.

Abstract

Upon nutritional limitation, the bacterium Bacillus subtilis has the capability to enter the irreversible process of sporulation. This developmental process is bistable, and only a subpopulation of cells actually differentiate into endospores. Why a cell decides to sporulate or not to do so is poorly understood. Here, through the use of time-lapse microscopy, we follow the growth, division, and differentiation of individual cells to identify elements of cell history and ancestry that could affect this decision process. These analyses show that during microcolony development, B. subtilis uses a bet-hedging strategy whereby some cells sporulate while others use alternative metabolites to continue growth, providing the latter subpopulation with a reproductive advantage. We demonstrate that B. subtilis is subject to aging. Nevertheless, the age of the cell plays no role in the decision of its fate. However, the physiological state of the cell's ancestor (more than two generations removed) does affect the outcome of cellular differentiation. We show that this epigenetic inheritance is based on positive feedback within the sporulation phosphorelay. The extended intergenerational “memory” caused by this autostimulatory network may be important for the development of multicellular structures such as fruiting bodies and biofilms.