Bacteria-phage interactions are important because they directly impact microbial diversity, which ultimately determines how ecosystems function and respond to environmental change (1). CRISPR-Cas, an adaptive immune system found in bacteria and archaea, has been shown to influence these interactions. We recently demonstrated that CRISPR can rapidly remove phage from the environment (2). This effect is contingent on the generation of population-level diversity within the CRISPR locus, which limits the ability of phage to evolve to overcome the immune response (2). However, natural phage populations may be more genetically diverse compared to the clonal phage populations used in most laboratory experiments, and theory suggests that this may greatly reduce the benefit of CRISPR diversity (3). To examine this hypothesis, we exposed bacteria to phage populations with different levels of genetic diversity, and measured how this impacts the evolution of CRISPR immunity and its associated benefit. We show that genetically diverse phage populations are more able to overcome CRISPR immune responses, and as a consequence phage diversity can tip the balance in the evolution of host resistance from CRISPR to surface-based resistance (i.e. receptor modification or loss). These data identify a crucial ecological variable that impacts the evolution of CRISPR immunity and these findings are of particular relevance to fields such as phage therapy and environmental prophylaxis where it is important to predict and manipulate the evolutionary response of a target population (4).

(1) Bell et al, 2005, Nature. (2) van Houte et al, Nature, 2016. (3) Iranzo et al, 2013, J. Bacteriol. (4) Levin, Bull, 2004, Nat. Rev. MBio.