Bacterial phenotypic heterogeneity through the lens of single-cell RNA sequencing

Bacterial transcription is not monolithic. Microbes exist in a wide variety of cell states that help them adapt to their environment, acquire and produce essential nutrients, and engage in both competition and cooperation with their neighbors. While we typically think of bacterial adaptation as a group behavior, where all cells respond in unison, there is often a mixture of phenotypic responses within a bacterial population, where distinct cell types arise. A primary phenomenon driving these distinct cell states is transcriptional heterogeneity. Given that bacterial mRNA transcripts are extremely short-lived compared to eukaryotes, their transcriptional state is closely associated with their physiology, and thus the transcriptome of a bacterial cell acts as a snapshot of the behavior of that bacterium. Therefore, the application of single-cell transcriptomics to microbial populations will provide novel insight into cellular differentiation and bacterial ecology. In this review, we provide an overview of transcriptional heterogeneity in microbial systems, discuss the findings already provided by single-cell approaches, and plot new avenues of inquiry in transcriptional regulation, cellular biology, and mechanisms of heterogeneity that are made possible when microbial communities are analyzed at single-cell resolution.