Abstract
Diversity in host resistance often associates with reduced pathogen spread. This may result from ecological and evolutionary processes, likely with feedback between them. Theory and experiments on bacteria-phage interactions have shown that genetic diversity of the bacterial adaptive immune system can limit phage evolution to overcome resistance. Using the CRISPR-Cas bacterial immune system and lytic phage, we engineered a host-pathogen system where each bacterial host genotype could be infected by only one phage genotype. With this model system, we explored how CRISPR diversity impacts the spread of phage when they can overcome a resistance allele, how immune diversity affects the evolution of the phage to increase its host range and if there was feedback between these processes. We show that increasing CRISPR diversity benefits susceptible bacteria via a dilution effect, which limits the spread of the phage. We suggest that this ecological effect impacts the evolution of novel phage genotypes, which then feeds back into phage population dynamics.
Highlights
Genetic diversity is a key determinant of the ecology and evolution of host-pathogen systems
To explore how population-level immune diversity would influence the population dynamics and evolution of an infective phage and its susceptible host genotype, we first developed a library of 24 P. aeruginosa PA14 bacteriophage-insensitive mutants (BIMs), and a corresponding library of 24 DMS3vir mutants, each of which was preevolved to infect only one of the 24 host BIMs
Because this experimental design increases the proportion of resistant bacterial hosts while decreasing the proportion of the susceptible host (Figure S1), it enables us to explicitly test how this dilution effect is related to the benefits of host CRISPR allele diversity
Summary
Genetic diversity is a key determinant of the ecology and evolution of host-pathogen systems. Various studies of wild organisms have shown that genetic diversity within a host species often affects pathogen prevalence. The importance of diversity for disease prevalence in wild populations has been observed in numerous species, for example: cheetahs (O'Brien et al, 1985); Italian agile frogs (Pearman & Garner, 2005); crimson rosella parrots (Eastwood et al, 2017); inbred black-footed ferret populations (Thorne & Williams, 1988); inbred California sea lions The importance of diversity for limiting disease in agricultural contexts has long been recognised (Elton, 1958), for example in rice (Zhu et al, 2000) and hybridising populations of honeybees Two recent metaanalyses have shown that host diversity is a robust defence against pathogens both in agricultural (Reiss & Drinkwater, 2018) and natural populations (Ekroth et al., 2019)
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