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Bacteria employ diverse strategies to defend against phage infection. Here, Gao and Wassarman et al. show at the atomic level how a bacterial pathway called qatABCD repurposes a nucleoside biosynthesis enzyme to control antiphage immunity.

Biochemical and structural studies show that the bacterial dGTPase CloA is activated by virally produced dTTP and inhibited by 5′-triphosphothymidyl-3′5′-thymidine produced by its regulatory partner CloB, and thereby balances antiviral defence and immune-mediated toxicity.

A Gifsy-1 prophage–encoded higher eukaryotes and prokaryotes nucleotide-binding protein, HepS, senses Siphoviridae infection, activates abortive defence by cleaving host transfer RNAs, blocks rival phages and avoids self-targeting via tail-tip variation.

Hailong, an anti-phage defence system, synthesizes an oligodeoxyadenylate signal that blocks effector activity in the absence of phage infection but is degraded by phage-encoded DNA exonucleases, leading to protective growth arrest of infected cells.

Caspase recruitment domains (CARDs) are present in defence systems that protect bacteria against phage, where the bacterial CARD domain is essential for protease-mediated activation of bacterial gasdermins that promote cell death.

Cells use specialized nucleotide signals to activate defences. A bacterial study reveals a previously unknown class of signals, formed by linking molecules of ATP and S-adenosyl methionine.

TREX1 is a cytosolic DNA nuclease and the genetic mutations of it are linked to autoimmune diseases. Here the authors determine the first structure of the human TREX1–DNA complex, and provide a new foundation to explain how patient TREX1 mutations cause autoimmune disease.

A bacterial family of cGAS/DncV-like nucleotidyltransferases synthesizes a diverse range of cyclic dinucleotide and trinucleotide compounds that are likely to modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.

The authors identify Drosophila cGLR1 as a double-stranded RNA sensor and 3′2′-cGAMP as a nucleotide second messenger and activator of Drosophila STING signalling.

Structures of prokaryotic homologues of STING permit the reconstruction of the evolutionary trajectory of its incorporation into metazoan innate immunity, and reveal a role for the conserved cGAS–STING pathway in prokaryotic defence against bacteriophages.

In response to phage infection, the Toll/interleukin-1 receptor (TIR) domain protein ThsB of the type II Thoeris defence system produces histidine conjugated to ADP-ribose, which stimulates bacterial defence by interacting with the Macro domain of the ThsA membrane effector protein.

X-ray crystallography, cryo-EM and biochemical analysis provide insight into the assembly of the bacterial Gabija complex, an anti-phage system, and reveal how viruses can evade this defence mechanism.

We identified Tad1, a large family of phage-encoded proteins that inhibit Thoeris immunity, and define the chemical structure of a central immune signalling molecule, showing a new mode of action by which pathogens can suppress host immunity.

A study using a biochemical screen of 57 phages in two bacterial species identifies and characterizes proteins enabling phages to evade CBASS and Pycsar immune systems, and describes the mechanisms involved.

Through structural analysis of the activation of bacterial STING, the molecular basis of STING filament formation and TIR effector domain activation in antiphage signalling is defined.

Cryo-electron microscopy and molecular dynamics studies of a Vitiosangium gasdermin pore reveal insights into the assembly of this large and diverse family of membrane pore-forming proteins.

Poxvirus immune nucleases (poxins) degrade 2′,3′-cyclic GMP–AMP that is produced by cyclic GMP–AMP synthase (cGAS) to evade the innate immune system of the host.

The structure of the Cas1–Cas2 complex bound to a protospacer sequence illustrates how foreign DNA is captured and measured by bacterial proteins in preparation for integration into CRISPR loci.

A study reports the discovery and characterization of four distinct families of phage-encoded anti-defence proteins that inhibit a variety of bacterial defence systems.

C-to-Ψ conversion is a previously uncharacterized form of base editing. Here, the authors describe how the TrcP enzyme catalyzes this process in a stepwise fashion and how this editing process is controlled by a network of modifications and nutrient availability to optimize translation efficiency.

Plasmodium vivax, the leading cause of human malaria in Asia and Latin America, is thought to have an Asian origin. Here, the authors show that wild chimpanzees and gorillas in Africa are infected with parasites that are closely related to P. vivax, indicating an African origin for this species.

The CRISPR–Cas system mediates immunity to foreign DNA sequences that are integrated as spacers between repeats in the CRISPR locus. Work from Doudna and colleagues shows that nucleases Cas1 and Cas2 form a stable complex that recognizes the CRISPR leader-repeat sequence, thus determining the site of integration.

The evolutionary origin of the human malaria parasite Plasmodium falciparum has been much debated. Genetic analysis of a large number of faecal samples from wild-living African apes now shows that Plasmodium parasites from Western gorillas are most closely related to the human parasite. The data suggest that human P. falciparum evolved from a gorilla parasite after a single host transfer event.

Eukaryotic initiation factor 3 (eIF3)—the deregulation of which has been linked with diverse cancers—is shown to bind to and direct the specialized translation of a subset of messenger RNAs, primarily involved in cell proliferation, differentiation and apoptosis, and can exert either translational activation or repression.

The initiation protein eIF3d serves as an alternative cap-recognition factor for a subclass of mRNAs, such as c-Jun; the high-resolution structure of the eIF3d cap-binding domain can be modelled onto the cap structure, defining interactions that are needed for translation of these mRNAs.