Bacterial biodiversity drives the evolution of CRISPR-based phage resistance

About half of all bacteria carry genes for CRISPR-Cas adaptive immune systems¹, which provide immunological memory by inserting short DNA sequences from phage and other parasitic DNA elements into CRISPR loci on the host genome². Whereas CRISPR loci evolve rapidly in natural environments^3,4, bacterial species typically evolve phage resistance by the mutation or loss of phage receptors under laboratory conditions^5,6. Here we report how this discrepancy may in part be explained by differences in the biotic complexity of in vitro and natural environments^7,8. Specifically, by using the opportunistic pathogen Pseudomonas aeruginosa and its phage DMS3vir, we show that coexistence with other human pathogens amplifies the fitness trade-offs associated with the mutation of phage receptors, and therefore tips the balance in favour of the evolution of CRISPR-based resistance. We also demonstrate that this has important knock-on effects for the virulence of P. aeruginosa, which became attenuated only if the bacteria evolved surface-based resistance. Our data reveal that the biotic complexity of microbial communities in natural environments is an important driver of the evolution of CRISPR-Cas adaptive immunity, with key implications for bacterial fitness and virulence.