The impact of bottlenecks on microbial survival, adaptation, and phenotypic switching in host-pathogen interactions.

Microbial pathogens and viruses can often maintain sufficient population diversity to evade a wide range of host immune responses. However, when populations experience bottlenecks, as occurs frequently during initiation of new infections, pathogens require specialized mechanisms to regenerate diversity. We address the evolution of such mechanisms, known as stochastic phenotype switches, which are prevalent in pathogenic bacteria. We analyze a model of pathogen diversification in a changing host environment that accounts for selective bottlenecks, wherein different phenotypes have distinct transmission probabilities between hosts. We show that under stringent bottlenecks, such that only one phenotype can initiate new infections, there exists a threshold stochastic switching rate below which all pathogen lineages go extinct, and above which survival is a near certainty. We determine how quickly stochastic switching rates can evolve by computing a fitness landscape for the evolutionary dynamics of switching rates, and analyzing its dependence on both the stringency of bottlenecks and the duration of within-host growth periods. We show that increasing the stringency of bottlenecks or decreasing the period of growth results in faster adaptation of switching rates. Our model provides strong theoretical evidence that bottlenecks play a critical role in accelerating the evolutionary dynamics of pathogens.