Diverse enzymatic activities mediate antiviral immunity in prokaryotes

TLDR

Bacteria and archaea frequently encounter viruses and rely on known defense systems such as restriction enzymes and CRISPR, yet the vast viral diversity implies many additional, yet undiscovered, antiviral mechanisms. We computationally predict a diverse set of additional putative defense genes that remain to be experimentally characterized. Our systematic gene prediction and heterologous reconstitution uncovered 29 widespread antiviral gene cassettes, present in 32 % of sequenced bacterial and archaeal genomes, that protect against specific bacteriophages and employ novel enzymatic activities such as RNA editing and retron satellite DNA synthesis, underscoring the immense molecular repertoire used by microbes to fight viruses.

Abstract

Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses.