CBASS to cGAS-STING: The Origins and Mechanisms of Nucleotide Second Messenger Immune Signaling DOI
Kailey M. Slavik, Philip J. Kranzusch

Annual Review of Virology, Год журнала: 2023, Номер 10(1), С. 423 - 453

Опубликована: Июнь 29, 2023

Host defense against viral pathogens is an essential function for all living organisms. In cell-intrinsic innate immunity, dedicated sensor proteins recognize molecular signatures of infection and communicate to downstream adaptor or effector activate immune defense. Remarkably, recent evidence demonstrates that much the core machinery immunity shared across eukaryotic prokaryotic domains life. Here, we review a pioneering example evolutionary conservation in immunity: animal cGAS-STING (cyclic GMP-AMP synthase-stimulator interferon genes) signaling pathway its ancestor bacteria, CBASS nucleotide-based antiphage system) We discuss unique mechanism by which cGLRs (cGAS-like receptors) bacterial CD-NTases (cGAS/dinucleotide-cyclase Vibrio (DncV)-like nucleotidyltransferases) these pathways link pathogen detection with activation using nucleotide second messenger signals. Comparing biochemical, structural, mechanistic details cGAS-STING, cGLR signaling, CBASS, highlight emerging questions field examine pressures may have shaped origins antiviral

Язык: Английский

An expanded arsenal of immune systems that protect bacteria from phages DOI Creative Commons
Adi Millman, Sarah Melamed, Azita Leavitt

и другие.

Cell Host & Microbe, Год журнала: 2022, Номер 30(11), С. 1556 - 1569.e5

Опубликована: Окт. 26, 2022

Язык: Английский

Процитировано

287
The highly diverse antiphage defence systems of bacteria DOI
Héloïse Georjon, Aude Bernheim

Nature Reviews Microbiology, Год журнала: 2023, Номер 21(10), С. 686 - 700

Опубликована: Июль 17, 2023

Язык: Английский

Процитировано

256
Phages and their satellites encode hotspots of antiviral systems DOI Creative Commons
François Rousset, Florence Depardieu, Solange Miele

и другие.

Cell Host & Microbe, Год журнала: 2022, Номер 30(5), С. 740 - 753.e5

Опубликована: Март 21, 2022

Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key elements their own benefit. Here, we show that E. coli P2-like and parasitic P4-like hotspots variation containing reservoirs anti-phage systems. We validate the activity describe PARIS, an abortive infection system triggered a phage-encoded anti-restriction protein. Antiviral participate in inter-viral competition shape dynamics between bacterial host, phages, satellites. Notably, can benefit helper phage during with virulent turning relationship into mutualistic one. Anti-phage present across distant species constitute substantial source mobile elements.

Язык: Английский

Процитировано

244
A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome DOI Creative Commons
Christopher N. Vassallo, Christopher R. Doering, Megan L. Littlehale

и другие.

Nature Microbiology, Год журнала: 2022, Номер 7(10), С. 1568 - 1579

Опубликована: Сен. 19, 2022

The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification CRISPR-Cas. Many additional anti-phage have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic context identify in 71 diverse E. coli strains. Our results unveil 21 conserved systems, none of which were previously detected as enriched islands. Additionally, our work indicates that intact prophages mobile genetic elements are primary reservoirs distributors coli, with typically carried specific locations or hotspots. These hotspots encode dozens uncharacterized system candidates. findings reveal extended landscape antiviral immunity provide approach for mapping other species.

Язык: Английский

Процитировано

221
Microbial defenses against mobile genetic elements and viruses: Who defends whom from what? DOI Creative Commons
Eduardo P. C. Rocha, David Bikard

PLoS Biology, Год журнала: 2022, Номер 20(1), С. e3001514 - e3001514

Опубликована: Янв. 13, 2022

Prokaryotes have numerous mobile genetic elements (MGEs) that mediate horizontal gene transfer (HGT) between cells. These can be costly, even deadly, and cells use defense systems to filter, control, or inactivate them. Recent studies shown prophages, conjugative elements, their parasites (phage satellites mobilizable elements), other poorly described MGEs encode homologous those of bacteria. constitute a significant fraction the repertoire cellular genes. As components MGEs, these presumably evolved provide them, not cell, adaptive functions. While interests host are aligned when they face common threat such as an infection by virulent phage, defensive functions carried might also play more selfish roles fend off antagonistic ensure maintenance in cell. eventually lost from surviving genomes mutational processes co-opted advantage The abundance thus sheds new light on role, effect, fate so-called “cellular systems,” whereby only merely microbial weapons 2-partner arms race, but tools intragenomic conflict multiple with divergent shape cell flow at population level.

Язык: Английский

Процитировано

150
Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome DOI Creative Commons
Matthew G. Durrant, Alison Fanton, Josh Tycko

и другие.

Nature Biotechnology, Год журнала: 2022, Номер 41(4), С. 488 - 499

Опубликована: Окт. 10, 2022

Abstract Large serine recombinases (LSRs) are DNA integrases that facilitate the site-specific integration of mobile genetic elements into bacterial genomes. Only a few LSRs, such as Bxb1 and PhiC31, have been characterized to date, with limited efficiency tools for in human cells. In this study, we developed computational approach identify thousands LSRs their attachment sites, expanding known LSR diversity by >100-fold enabling prediction insertion site specificities. We tested recombination activity cells, classifying them landing pad, genome-targeting or multi-targeting LSRs. Overall, achieved up seven-fold higher than genome efficiencies 40–75% cargo sizes over 7 kb. also demonstrate virus-free, direct plasmid amplicon libraries improved functional genomics applications. This systematic discovery directly from microbial sequencing data provides resource 60 experimentally cells large-payload without exposed double-stranded breaks.

Язык: Английский

Процитировано

134
PADLOC: a web server for the identification of antiviral defence systems in microbial genomes DOI Creative Commons
Leighton Payne, Sean Meaden, Mario Rodríguez Mestre

и другие.

Nucleic Acids Research, Год журнала: 2022, Номер 50(W1), С. W541 - W550

Опубликована: Май 6, 2022

Most bacteria and archaea possess multiple antiviral defence systems that protect against infection by phages, archaeal viruses mobile genetic elements. Our understanding of the diversity has increased greatly in last few years, many more likely await discovery. To identify defence-related genes, we recently developed Prokaryotic Antiviral Defence LOCator (PADLOC) bioinformatics tool. increase accessibility PADLOC, describe here PADLOC web server (freely available at https://padloc.otago.ac.nz), allowing users to analyse whole genomes, metagenomic contigs, plasmids, phages viruses. The includes a than 5-fold system types detected (since first release) expanded functionality enabling detection CRISPR arrays retron ncRNAs. Here, provide user information such as input options, description outputs, limitations considerations for interpretation results, guidance subsequent analyses. also houses precomputed database > 230,000 RefSeq genomes. These data reveal two taxa, Campylobacterota Spriochaetota, with unusual abundance. Overall, provides convenient accessible resource systems.

Язык: Английский

Процитировано

123
Phage–host coevolution in natural populations DOI

Damien Piel,

Maxime Bruto, Yannick Labreuche

и другие.

Nature Microbiology, Год журнала: 2022, Номер 7(7), С. 1075 - 1086

Опубликована: Июнь 27, 2022

Язык: Английский

Процитировано

122
Discovery of phage determinants that confer sensitivity to bacterial immune systems DOI Creative Commons
Avigail Stokar-Avihail,

Taya Fedorenko,

Jens Hör

и другие.

Cell, Год журнала: 2023, Номер 186(9), С. 1863 - 1876.e16

Опубликована: Апрель 1, 2023

Язык: Английский

Процитировано

107
Bacteriophages inhibit and evade cGAS-like immune function in bacteria DOI Creative Commons
Erin Huiting, Xueli Cao, Jie Ren

и другие.

Cell, Год журнала: 2023, Номер 186(4), С. 864 - 876.e21

Опубликована: Фев. 1, 2023

A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2′,3′-cGAMP and activates effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether harboring CBASS antagonize co-evolve with phages is unknown. Here, we identified an endogenous enzyme in Pseudomonas aeruginosa generates 3′,3′-cGAMP during phage infection, signals to a phospholipase effector, limits replication. In response, express anti-CBASS protein ("Acb2") forms hexamer three molecules reduces activity. Acb2 also binds produced by other bacterial (3',3'-cUU/UA/UG/AA) mammalian (2′,3′-cGAMP), suggesting broad inhibition cGAS-based immunity. Upon deletion, blocks lytic replication lysogenic induction, but rare evade major capsid gene mutations. Altogether, demonstrate function strategies evasion.

Язык: Английский

Процитировано

90