Phenotypic heterogeneity between genetically identical cells permits growth with lethal levels of formaldehyde stress

Scientists tend to appreciate microbes for their simplicity and predictability: a population of genetically identical cells inhabiting a uniform environment is expected to behave in a uniform way. However, counter-examples to this assumption are frequently being discovered, forcing a re-examination of the relationship between genotype and phenotype. In most such examples, bacterial cells are found to split into two discrete populations, for instance growing and non-growing. Here, we report the discovery of a novel example of microbial phenotypic heterogeneity in which cells are distributed along a gradient of phenotypes, ranging from low to high tolerance of a toxic chemical. Furthermore, we demonstrate that the distribution of phenotypes changes in different growth conditions, and we use mathematical modeling to show that cells may change their phenotype either randomly or in a particular direction in response to the environment. Our work expands our understanding of how a bacterial cell's genome, family history, and environment all contribute to its behavior, with implications for the diverse situations in which we care to understand the growth of any single-celled populations.