Systematic discovery of antiphage defense systems in the microbial pangenome

TLDR

Bacteria and phages engage in an arms race that has produced sophisticated antiphage defense systems, such as CRISPR‑Cas and restriction‑modification, and these systems are often clustered in defense islands within microbial genomes. The study aims to comprehensively characterize bacterial antiphage defenses by analyzing gene families adjacent to known defense genes. The authors examined gene families near known defense genes and then engineered and validated candidate systems in model bacteria to test antiphage activity. They identified nine novel antiphage systems and one antiplasmid system that are widespread and highly protective, including flagella‑ and condensin‑based systems, and the data suggest a shared ancient ancestry of innate immunity components across animals, plants, and bacteria.

Abstract

The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria.