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Ye et al. define the structure and mechanisms of a bacterial pathway that performs ubiquitination-like protein conjugation, revealing new insights into the evolution and biological roles of ubiquitina...

Bacteria are frequently attacked by viruses, known as phages, and rely on diverse defence systems like restriction endonucleases and CRISPR-Cas to survive. While phages can evade these defences by cov...

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After sensing capsids, the Thoeris antiphage defense system triggers a cascade that leads to NAD+ cleavage and cell arrest, which are dynamics that are mirrored in some mammalian immune pathways.

Proximity-ligation-based sequencing from 111 samples and 5 environments reveals that a substantial proportion of phages infect multiple species.

Recognition of exogenous RNA by Toll-like receptors (TLRs) is central to pathogen defense. Using two distinct binding pockets, TLR7 and TLR8 recognize…

Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...

Human host-associated cellular products may act as induction agents for bacteriophages.

The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.

Phage defense systems in bacteria exhibit high degrees of modularity, with sensing, signal transmission, and effector enzymes frequently being exchanged among phage defense gene clusters. In this study, we capitalized on this modularity to discover phage defense systems by searching for defense-associated modules in new gene contexts. This approach revealed a large and interconnected network of modular components distributed across diverse gene clusters. From over 500 candidate defense systems, we selected nine for experimental testing and validated three: Dionysus, a TerB-encoding system that disrupts early phage infection vesicle formation by Jumbo phages; Ophion, a Radical SAM-containing system that prevents the formation of the Jumbo phage nucleus; and Ambrosia, a tightly regulated RM-like system. Collectively, we demonstrate that leveraging the modular architecture of phage defense systems is an effective approach to their discovery. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, 101003229 Netherlands Organisation for Scientific Research, VI.C.192.027, OCENW.XS23.1.006 Koningin Wilhelmina Fonds, 15602

ERC Starting Grant awarded to Jens Hör from the Helmholtz Institute Würzburg

Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...

Multiple bacterial immune systems, including CBASS, Thoeris, and Pycsar, employ signaling molecules that activate the immune response following phage infection. Phages counteract bacterial immune sign...