Exploring the role of diversity in bacteria-phage ecology and evolution

Abstract

Host diversity is one of the key factors that determine why pathogens can emerge and cause epidemics, the scale of an epidemic, and host-pathogen coevolution. Although the effects of host diversity on pathogen spread are well-described, we currently lack a detailed understanding of the ecological and evolutionary mechanisms that underpin them. The interactions between phage and bacteria with a CRISPR-Cas immune system are a tractable model system to study how host density and genetic diversity impacts phage epidemiology, evolution and coevolution between the host and the phage. In this thesis, I first summarize existing literature on the role of host genetic diversity on host-parasite interactions. I then present experiments that explore how population bottlenecks, which impact both host density and genetic diversity, affect the epidemiology and evolution of phage. I find that bottlenecks result in more rapid phage extinction, which is driven primarily by the changes in host density. Next, I explore how manipulations of host genetic diversity alter the epidemiology and evolution of a phage that can infect a single host genotype in the population. I find that greater diversity results in protection of the susceptible host due to reduced contact rates with phage. I also find evidence for interaction between host diversity, phage population size, and the likelihood of phage evolution. Finally, I examine the coevolutionary interaction between phage and bacteria with CRISPR immune systems. I find that bacterial populations initially evolve diversity in their CRISPR-Cas immune systems that is sufficiently low for an escalating arms-race dynamic to ensue, that lasts until diversity in the CRISPR-Cas resistance alleles becomes too high, causing phage extinction.