What are the benefits of phenotypic heterogeneity? The ability of bacterial populations to develop phenotypically heterogeneous subpopulations has been recognized for decades. A recent study found that genetic hallmarks of phenotypic heterogeneity are ubiquitous among bacterial species of the intestinal microbiota, underscoring that this is a broadly employed, underappreciated survival strategy for both pathogenic and commensal bacterial species. Phenotypic heterogeneity—functional diversity among genetically identical cells—can permit division of labor and cooperative behaviors or serve as a bet-hedging strategy to help ensure the survival of the population as a whole. Division of labor occurs when biological processes are separated among subpopulations, conferring an overall fitness advantage to the population. For example, the opportunistic pathogen Pseudomonas aeruginosa forms multiple unique cell types that perform specialized roles in the formation of biofilm. Some cells contribute to biofilm extracellular matrix production and initiate biofilm development, while others exhibit surface motility and allow biofilm expansion. In the bet-hedging strategy, incorporating phenotypic variants into a population increases the likelihood that some members will survive a stress. In settings where environmental changes are rapid and stark, phenotypic heterogeneity helps ensure the survival of the population at the expense of individuals not well suited to the current environment, which are selected against and lost. This strategy is advantageous over traditional sense-and-respond mechanisms, which require an adaptation time that may be insufficient in the face of sudden or severe environmental changes. Mechanisms of phenotypic heterogeneity may be particularly important in the context of disease, as these mechanisms are more common in host-associated bacteria than in aquatic or terrestrial species
