The evolutionary success of regulated cell death in bacterial immunity

Bacteria employ a complex arsenal of immune mechanisms to defend themselves against phages. Recent studies demonstrate that these immune mechanisms frequently involve regulated cell death in response to phage infection. By sacrificing infected cells, this strategy prevents the spread of phages within the surrounding population. In this review, we discuss the principles of regulated cell death in bacterial defense, and show that over 70% of sequenced prokaryotes employ this strategy as part of their defensive arsenals. We highlight the modularity of defense systems involving regulated cell death, explaining how shuffling between phage-sensing and cell-killing protein domains dominates their evolution. Some of these defense systems are the evolutionary ancestors of key components of eukaryotic immunity, highlighting their importance in shaping the evolutionary trajectory of immune systems across the tree of life.