Division of labor in bacteria The emergence of subpopulations that perform distinct metabolic roles has been observed in populations of genetically identical bacteria.

W hy do we have so many different types of cells in our body? A plausible explanation is that a single cell can only perform a limited number of roles at the same time. As a consequence, our body consists of more than 200 clearly distinguishable types of cells (Heintzman et al., 2009). But what about smaller life forms such as bacteria? These microbes often form communities of genetically identical, or clonal, cells that can collectively activate genes or regulate metabolic processes. It remains unclear, however, whether each single cell performs all the roles observed at the population level, or whether cells specialize on a subset of these functions. Although a division of labor has been suspected, evidence remains scant (Nikolic et al., 2013; de Lorenzo et al., 2015; Ackermann, 2015). Now, in eLife, Michael Elowitz of the California Institute of Technology and colleagues – including Adam Rosenthal as first author – report how a clonal population of Bacillus subtilis bacteria divides into two subpopulations with distinct roles (Rosenthal et al., 2018). The two groups of bacteria likely arose from a phenomenon known as stochastic gene expression. This happens when the randomness associated with the transcription and translation of genes is amplified by the cell’s regulatory network, and results in cells with identical genomes having different traits or phenotypes (Elowitz et al., 2002). While many cases of stochastic gene expression have been described in the last decade, two aspects set this study apart from previous work (Kaern et al., 2005): first, the two subpopulations engaged in metabolic interactions; second, the composition of the population changed dynamically over time (Figure 1). Rosenthal et al. – who are based at Caltech and Princeton University – grew several populations of B. subtilis on two sugars, glucose and malate, and observed that some bacteria did not metabolize these sugars completely, but instead began secreting acetate, a metabolic intermediate. Secreting acetate can help bacteria to grow more quickly, but it can also accumulate to toxic levels (Pfeiffer et al., 2001). The researchers found that this toxicity was remediated by a small subpopulation of bacteria that started to convert acetate to acetoin, which is harmless, thus enabling the population to grow in a detoxified environment. These acetate-consuming cells only emerged after the acetate-producing cells arose, as a direct response to the accumulating toxicity. This demonstrates that individual cells in a population of genetically identical bacteria can activate alternative metabolic pathways that affect the population as a whole. The study of Rosenthal et al. raises an intriguing question: does a metabolic division of labor happen often in clonal populations of bacteria? There are reasons to assume that it would be beneficial and therefore potentially widespread. For example, recent studies suggest that bacteria can divide up to 20% faster if they trade certain cellular ’building blocks’ with other bacterial species, instead of producing them on their own Copyright Dal Co et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Related research article Rosenthal AZ, Qi Y, Hormoz S, Park J, Li SH, Elowitz MB. 2018. Metabolic interactions between dynamic bacterial subpopulations. eLife 7: e33099. DOI: 10.7554/eLife.33099