Abstract
Shifts in microbial strain structure underlie both emergence of new pathogens and shifts in patterns of infection and disease of known agents. Understanding the selective pressures at a population level as well as the mechanisms at the molecular level represent significant gaps in our knowledge regarding microbial epidemiology. Highly antigenically variant pathogens, which are broadly represented among microbial taxa, are most commonly viewed through the mechanistic lens of how they evade immune clearance within the host. However, equally important are mechanisms that allow pathogens to evade immunity at the population level. The selective pressure of immunity at both the level of the individual host and the population is a driver of diversification within a pathogen strain. Using Anaplasma marginale as a model highly antigenically variable bacterial pathogen, we review how immunity selects for genetic diversification in alleles encoding outer membrane proteins both within and among strains. Importantly, genomic comparisons among strains isolated from diverse epidemiological settings elucidates the counterbalancing pressures for diversification and conservation, driven by immune escape and transmission fitness, respectively, and how these shape pathogen strain structure.