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viernes, 26 de enero de 2018

Nuevos sistemas de defensa frente a fagos en bacterias

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 unknown defense systems are located in “defense islands” in microbial genomes. 

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.

Bacteria and archaea are frequently attacked by viruses (phages), and as a result have developed multiple, sophisticated lines of active defense (13) that can collectively be referred to as the prokaryotic “immune system.” Antiphage defense strategies include restriction-modification (R-M) systems that target specific sequences on the invading phage (4), CRISPR-Cas, which provides acquired immunity through memorization of past phage attacks (5), abortive infection systems (Abi) that lead to cell death or metabolic arrest upon infection (6), and additional systems whose mechanism of action is not yet clear such as BREX (7), prokaryotic Argonautes (pAgos) (8) and DISARM (9). Different bacteria encode different sets of defense systems: CRISPR-Cas systems are found in about 40% of all sequenced bacteria (1011), R-M systems are found in about 75% of prokaryote genomes (12) while pAgos and BREX appear in about 10% (713). It has been suggested that many currently unknown defense systems reside in genomes and plasmids of nonmodel bacteria and archaea and await discovery (214).
Antiphage defense systems were found to be frequently physically clustered in bacterial and archaeal genomes such that, for example, genes encoding restriction enzymes commonly reside in the vicinity of genes encoding abortive infection systems and other phage resistance systems (1415). The observation that defense systems are clustered in genomic “defense islands” has led to the suggestion that genes of unknown function residing within such defense islands may also participate in antiphage defense (1516). Indeed, recent studies that focused on individual genes enriched next to known defense genes resulted in the discovery of new systems that protect bacteria against phages (7917).



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