Structure-functional characterization of Lactococcus AbiA phage defense system

Nucleic Acids Research, Год журнала: 2024, Номер 52(8), С. 4723 - 4738

Опубликована: Апрель 8, 2024

Abstract Bacterial reverse transcriptases (RTs) are a large and diverse enzyme family. AbiA, AbiK Abi-P2 abortive infection system (Abi) RTs that mediate defense against bacteriophages. What sets Abi apart from other RT enzymes is their ability to synthesize long DNA products of random sequences in template- primer-independent manner. Structures representatives have recently been determined, but there no structural data available for AbiA. Here, we report the crystal structure Lactococcus AbiA polymerase complex with single-stranded polymerization product. comprises three domains: an RT-like domain, helical domain typical polymerases, higher eukaryotes prokaryotes nucleotide-binding (HEPN) common many antiviral proteins. forms dimer distinguishes it Abi-P2, which form trimers/hexamers. We show activity vitro assay demonstrate requires presence HEPN enzymatically inactive. validate our biochemical results vivo through bacteriophage assays. Finally, suggest AbiA-mediated phage may not rely on cell death.

Язык: Английский

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Tail assembly interference is a common strategy in bacterial antiviral defenses

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 30, 2024

Many bacterial immune systems recognize phage structural components to activate antiviral responses, without inhibiting the function of component. These can be encoded in specific chromosomal loci, known as defense islands, and mobile genetic elements such prophages phage-inducible islands (PICIs). Here, we identify a family systems, named Tai (for 'tail assembly inhibition'), that is prevalent PICIs, P4-like satellites. protect their host population from other phages by blocking tail step, leading release tailless incapable infecting new hosts. To prevent autoimmunity, some Tai-positive have an associated counter-defense mechanism expressed during lytic cycle allows for formation. Interestingly, genes are organized non-contiguous operon, enabling coordinated expression.

Язык: Английский

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DNA end sensing and cleavage by the Shedu anti-phage defense system

Cell, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

The detection of molecular patterns associated with invading pathogens is a hallmark innate immune systems. Prokaryotes deploy sophisticated host defense mechanisms in anti-phage immunity. Shedu single-component system comprising putative nuclease SduA. Here, we report cryoelectron microscopy (cryo-EM) structures apo- and double-stranded DNA (dsDNA)-bound tetrameric SduA assemblies, revealing that the N-terminal domains form clamp recognizes free ends. End binding positions over PD-(D/E)XK domain, resulting dsDNA nicking at fixed distance from 5' end. end-directed activity prevents propagation linear vivo. Finally, show phages escape immunity by suppressing their recombination-dependent replication pathway. Taken together, these results define antiviral mechanism systems, underlining paradigm recognition pathogen-specific nucleic acid conserved feature across all life.

Язык: Английский

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Phage-Defense Systems Are Unlikely to Cause Cell Suicide

Viruses, Год журнала: 2023, Номер 15(9), С. 1795 - 1795

Опубликована: Авг. 24, 2023

As new phage-defense systems (PDs) are discovered, the overlap between their mechanisms and those of toxin/antitoxin (TAs) is becoming clear in that both use similar means to reduce cellular metabolism; for example, have members deplete energetic compounds (e.g., NAD+, ATP) nucleic acids, inflict membrane damage. Moreover, TAs PDs rather than altruistically killing host limit phage propagation (commonly known as abortive infection), metabolism since phages propagate less slow-growing cells, slow growth facilitates interaction multiple systems.

Язык: Английский

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Discovery and characterisation of new phage targeting uropathogenic Escherichia coli

Virology, Год журнала: 2024, Номер 597, С. 110148 - 110148

Опубликована: Июнь 20, 2024

Antimicrobial resistance is an escalating threat with few new therapeutic options in the pipeline. Urinary tract infections (UTIs) are one of most prevalent bacterial globally and prone to becoming recurrent antibiotic resistant. We discovered characterized six novel Autographiviridae Guernseyvirinae viruses (phage) against uropathogenic Escherichia coli (UPEC), a leading cause UTIs. The phage genomes were between 39,471 bp - 45,233 bp, 45.0% 51.0% GC%, 57 84 predicted coding sequences per genome. show that tail fiber domain structure, host capsule type, antiphage repertoire correlate range. In vitro characterisation cocktails showed synergistic improvement mixed UPEC strain population when sequentially dosed. Together, these set extending available treatments for UTI from UPEC, vM_EcoM_SHAK9454 represents promising candidate further through engineering.

Язык: Английский

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