How bacteria defend against their viruses and how viruses fight back? The tale of CRISPR-Cas versus anti-CRISPR
Department of Infection, Immunity, and Inflammation, Paris, France
Bacteria are under constant threat from their viruses (known as phages) which led to the evolution of a large repertoire of resistance mechanisms, amongst which ‘CRISPR-Cas’ is one of the most widespread. This immune system captures elements from the invader’s genome (spacers) and insert them into CRISPR loci to provide sequence-specific immunity against (re)infecting phages. The modalities of spacer acquisition allow the generation of high levels of spacer-diversity within bacterial populations, which is key to limit phage epidemics and evolution of escape mutations1. This CRISPR-mediated selection has likely driven the evolution of ‘anti-CRISPR’ (Acr) mechanisms in phage populations. Acr-phages have remarkable ecological dynamics: a first ‘sacrificial’ phage takes CRISPR-Cas defences down but fails to replicate, which allows a second phage to successfully multiply on this immunosuppressed host2. The benefits of Acr proteins may also be shared more largely in the phage community. Indeed, the immunosuppressed bacteria generated by Acr-phage infections can be exploited by other phages that lack acr genes3. These shared benefits depend on the ‘strength’ of the Acr and eventually impact the ecological dynamics of mixed phage populations. In addition to their ecological effects, Acr prevent the host from acquiring new spacers and hence inhibit the evolution of phage-resistance. Overall, the fitness benefits that CRISPR-Cas provide to bacteria, when they are exposed to predatory lytic phages, are annulled when phages encode Acr proteins3. To fight against Acr-phages, bacteria can deploy multiple defence mechanisms. We discovered in a P. aeruginosa clinical isolate, a novel innate immune system, coined Maestri, that acts in synergy with a CRISPR-Cas system to drive Acr-phage towards extinction4.
1. van Houte, S. et al. The diversity-generating benefits of a prokaryotic adaptive immune system. Nature 532, 385–388 (2016). 2. Landsberger, M. et al. Anti-CRISPR Phages Cooperate to Overcome CRISPR-Cas Immunity. Cell 174, 908-916.e12 (2018). 3. Chevallereau, A. et al. Exploitation of the Cooperative Behaviors of Anti-CRISPR Phages. Cell Host & Microbe 27, 189-198.e6 (2020).4. Maestri, A et al. unpublished