Expression level of anti-phage defence systems controls a trade-off between protection range and autoimmunity

The evolutionary arms race between bacteria and phages has given rise to elaborate anti-phage defence mechanisms. Although many of these systems have been characterized at the molecular level, the general principles and constraints at play are underexplored. It is broadly recognized that in addition to the protection they provide, these systems also bear a substantial cost. Here we identify an expression-dependent trade-off between the protection range of defence systems and the fitness burden they impose. We first focus on the SpbK system of Bacillus subtilis and then generalize to other systems across a range of bacteria. We show that increasing expression of defence systems enhances their protection range, and provide evidence that this is achieved by overwhelming phage strategies for circumventing bacterial defence. However, for most systems tested, increased expression also leads to self-inflicted toxicity. This trade-off between protection and autoimmunity may shape the evolution of regulatory strategies and favour the coexistence of multiple systems within a single genome.