Decoding Bistability and Drivers of Phenotypic Variation in Bacteria

In a process known as phenotypic heterogeneity or phenotypic variation, bacteria can produce distinct phenotypes within an isogenic population in response to shifting environmental conditions. Noise in gene expression, asymmetric cell division, phase variation, and quorum sensing are some of the mechanisms that contribute to this variability, which is maintained by gene regulatory networks (usually involving feedback loops). Bistability in gene regulatory networks generates subpopulations exhibiting specific traits that can contribute to more complex adaptive strategies, promoting the fitness of the bacterial community as a whole. This review explores recent examples of phenotypic heterogeneity and its functional importance in bacterial collective behaviors. We focus on how synthetic biology can be used to better understand bacterial gene regulatory networks and the mechanisms underlying antibiotic resilience and persistence, and we discuss the bistability of integrative and conjugative elements.