Phageptosis: A bacterial cell death program induced by crispr-cas systems.

Abstract

Programmed cell death (PCD) is a fundamental mechanism that has evolved across both unicellular and multicellular organisms for species preservation and self-protection. In certain contexts, genetically regulated cell death can enable surviving cells to thrive, safeguarding the genotype from extinction. Recent research on bacteria and archaea has revealed an ancient defense mechanism involving CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR-associated) proteins. These systems identify and eliminate invading genetic elements, such as bacteriophages, transposons, and plasmids, using sequence-specific RNA-guided targeting. A protease complex called Craspase, activated by non-self RNA, regulates Cas nuclease activity, facilitating this primitive form of immunity. Interestingly, this pathway shows structural and mechanistic similarities to apoptosis, the first recognized form of programmed mammalian cell death, characterized by chromatin condensation, nuclear fragmentation, and membrane blebbing. Other regulated cell death pathways, including necroptosis and pyroptosis, also share overlapping features. Comparative genomic studies reveal a conserved molecular framework underpinning these diverse death pathways across life forms. In this article, we explore the emerging parallels and distinctions between apoptosis and CRISPR-Cas-mediated cell death, a process we refer to as "phageptosis," highlighting evolutionary links and their implications for understanding cell death mechanisms.