Exploring the relationship between cell-cell communication and single-cell phenotypic heterogeneity in Pseudomonas aeruginosa

Clonal bacterial populations are genetically identical but contain many phenotypically distinct members. This heterogeneity mediates survival under rapidly changing conditions, and also provides a unique dimension to sociality in bacteria. Recent advancements in single-cell transcriptomics are beginning to shed light on the landscape of phenotypic cell states. Yet the specific drivers of variability and the functional roles of specific cell states are still poorly understood.

In this work, we explore a potential relationship between cell-cell variability and bacterial communication via quorum sensing (QS) in the opportunistic human pathogen Pseudomonas aeruginosa. Despite the conventional understanding that QS synchronizes gene expression at the group level, more advanced techniques have revealed single cell variation in QS receptor and synthase expression. We hypothesize that such variation can serve as a major driver of phenotypic heterogeneity in the hundreds of genes regulated by QS and define the social capacities of individual bacteria within a population. We also hypothesize that variation in QS capacities may play a role in protecting populations from exploitation by mutants that do not contribute to cooperation yet enjoy its benefits.

To test these hypotheses, we are employing seqFISH to characterize, with single cell resolution, the phenotypic heterogeneity within the QS network and define phenotypic cell states with regards to capacity for sociality. We aim to improve our understanding of the environment dependent dynamics of these cell states and use machine learning techniques to elucidate how certain cell states could potentially play a defensive role in the evolutionary stability of cooperative behavior.