Emerging tools for uncovering genetic and transcriptomic heterogeneities in bacteria

Bacterial communities display an astonishing degree of heterogeneities among their constituent cells across both the genomic and transcriptomic levels, giving rise to diverse social interactions and stress-adaptation strategies indispensable for proliferating in the natural environment (Ackermann in Nat Rev Microbiol 13:497-508, 2015). Our knowledge about bacterial heterogeneities and their physiological ramifications critically depends on our ability to unambiguously resolve the genetic and phenotypic states of the individual cells that make up the population. In this short review, I highlight several recently developed methods for studying bacterial heterogeneities, primarily focusing on single-cell techniques based on advanced sequencing and microscopy technologies. I will discuss the working principle of each technique as well as the types of problems each technique is best positioned to address. With significant improvements in resolution and throughput, these emerging tools together offer unprecedented and complementary views of various types of heterogeneities found within bacterial populations, paving the way for mechanistic dissections and systematic interventions in laboratory and clinical settings.