Growing cells in constant conditions at a fixed exponential growth rate in a shake flask — balanced growth — is arguably the most basic experiment in microbiology. We are so used to it that we sometimes forget to realise that this is not at all so obvious.
Not only the average growth rate remains fixed, but also the average cell size at birth and division. Either this emerges for free, and no active homeostatic mechanisms are required, or balanced growth requires evolved regulatory mechanisms. Analysis of experimental data, using a deceptively, simple theory, by Susan et al. , indicates that active homeostatic mechanisms are at work during steady-state growth and that without those balanced growth would be possible.
That cell-size homeostasis mechanisms exist and are required for balanced growth was already known — mostly from work by Suckjoon Jun’s lab. But what about growth-rate homeostasis? Do active mechanisms exist that maintain a constant average (and variance) of single-cell growth rate? Here we show that that is indeed the case for Bacillus subtilis.
We also found that its cell cycle is composed out of two phases. A first one, during which cells with variations in birth size correct size differences — they behave as “sizers” — and a second one during which cells behave as “timers” — they grow for a nearly fixed duration.
Our most surprising, and novel, finding was that cells experience a great disturbance of growth rate at division, with smaller cells outgrowing larger ones, while at division that growth rate variation has largely disappeared and growth rate became independent of cell size at birth.
So, also a growth-rate homeostasis mechanism is at work in Bacillus subtilis— like it is for cell size. How it works, we are currently figuring out.
You can find our paper here: https://www.cell.com/current-biology/fulltext/S0960-9822(20)30544-3.
- Susman, L., Kohram, M., Vashistha, H., Nechleba, J.T., Salman, H., andBrenner, N. (2018). Individuality and slow dynamics in bacterial growth ho-meostasis. Proc. Natl. Acad. Sci. USA 115, E5679–E5687.