Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death
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ABSTRACT:
PROVIDER: PRJEB42323 | ENA |
REPOSITORIES: ENA
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Project description:Bacteria deploy diverse antiphage defense systems, including small bioactive molecules providing protection at the multicellular level. DNA-intercalating anthracyclines such as daunorubicin exhibit broad antiphage activity, but the underlying mechanism had remained elusive. Here, we systematically screened the Escherichia coli BASEL phage collection to elucidate the mode of action of daunorubicin. We identified taxonomically distinct clusters of susceptible viral groups and demonstrate that daunorubicin blocks infection of T5-like phages (Markadamsvirinae) after first-step transfer (FST) as revealed by long-read sequencing. Continued expression of pre-early genes leads to abortive infection via ‘mutual destruction’, where both phage and host succumb. Analogous phenotypes of abortive infection were observed for taxonomically diverse phages with different DNA-intercalating antiphage molecules. Notably, we show that daunorubicin synergizes with downstream nucleic acid-targeting defences underscoring context dependency in the observed defense phenotype. Our findings reveal how chemical defense contributes to the multilayered antiviral immunity and highlight the intricate interplay between mechanistic inhibition and infection outcome.
2026-05-13 | PXD070949 | Pride
Project description:Discovery of the anti-phage activity of prokaryotic viperins
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Project description:Bacteria encode diverse defense systems including restriction-modification and CRISPR-Cas that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstrate many recently identified anti-phage defense operons are comprised of a nuclease and NTPase protein, suggesting additional nucleic acid targeting systems remain to be understood. Here we develop large-scale comparative cell biology and biochemical approaches to analyze 16 nuclease-NTPase systems and define molecular features that control anti-phage defense. Purification, biochemical characterization, and in vitro reconstitution of nucleic acid degradation demonstrates protein–protein complex formation is a shared feature of multi-gene nuclease-NTPase systems. We show that AbpAB, Hachiman, and PD-T4-8 system nucleases use highly degenerate recognition site preferences to enable broad nucleic acid degradation, and the Azaca system exhibits specific phage targeting through the recognition of modified phage genomic DNA. Our results uncover principles of anti-phage defense system function and highlight the mechanistic diversity of nuclease-NTPase systems in bacterial immunity.
2026-02-18 | GSE303276 | GEO
Project description:Viperin is an interferon-induced cellular protein conserved in animals. It was shown to inhibit the replication of multiple viruses by producing a ribonucleotide called 3’-deoxy-3’4’-didehydro-CTP (ddhCTP), which acts as a chain terminator for the viral RNA polymerase. Here we show that the eukaryotic viperin has originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins (pVips) produce a set of modified ribonucleotides that include, in addition to ddhCTP, also ddhGTP and ddhUTP. We further provide evidence that pVips protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting a conserved mechanism of action shared between pVips and the animal viperin. Our results unveil a potential repository of natural antiviral compounds produced by bacterial immune systems.
2020-08-24 | MTBLS1750 | MetaboLights
Project description: Not available
| S-EPMC6656896 | biostudies-literature
Project description:Quorum sensing (QS) is the cell density-dependent virulence factor regulator in Pseudomonas aeruginosa. Here, we elucidate PIT2, a phage-encoded inhibitor of the QS regulator LasR, derived from the lytic Pseudomonas phage LMA2. PIT2 inhibits the effectors PrpL and LasA of the type 2 secretion system of P. aeruginosa and attenuates bacterial virulence towards HeLa cells and in Galleria mellonella. Using RNAseq-based differential gene expression analysis, the effect of PIT2 on the LasR regulatory network was revealed. Moreover, the specific interaction between LasR and PIT2 was determined. These data expand our knowledge on phage-encoded modulators of the bacterial metabolism, as this examples an anti-virulence protein derived from a lytic phage. From an applied perspective, this phage protein reveals and exploits an interesting anti-virulence target in P. aeruginosa. As such, it lays the foundation for a new phage-inspired anti-virulence strategy to combat multidrug resistant pathogens and opens the door for SynBio applications.
2023-09-27 | GSE227677 | GEO
Project description:Bacteriophages are increasingly recognised as key players in modulating plant-microbe interactions, including their potential in the biocontrol of plant pathogenic bacteria. In this study, we investigated the tripartite interaction between, Arabidopsis thaliana, the bacterial plant pathogen Xanthomonas campestris pv. campestris (Xcc), and the lytic phage Seregon. Using meta-transcriptomic profiling, we characterized host and pathogen responses during infection and phage treatment. While a single phage treatment did not lead to the eradication of Xcc, treatment with phage Seregon significantly mitigated Xcc-induced disease symptoms, restoring leaf growth to levels comparable to the uninfected control within 14 days post-inoculation. Our data revealed that phage-mediated protection is associated with early bacterial recognition and suppression of jasmonate (JA)-related responses in the host. Analysis of nuclear localized reporter plant cell lines further confirmed a significant reduction in ROS levels in phage-treated plants. Concurrently, Xcc exhibited significant transcriptional downregulation of key virulence factors in the presence of the phage, including the genes encoding the type III secretion system, its associated effectors, and components involved in flagella biosynthesis. Remarkably, phage treatment did not lead to a significant increase in bacterial resistance to phage infection, which is in stark contrast to in vitro conditions. Taken together, this study provides first mechanistic insight into how phages can be harnessed to shape plant-pathogen interactions and highlights their potential role in enhancing plant resilience through targeted modulation of both host immunity and pathogen behaviour.
2025-04-17 | GSE294853 | GEO
Project description: Not available
| S-EPMC7045805 | biostudies-literature
Project description:Bacteriophages must overcome diverse bacterial immune systems, yet the molecular principles enabling such escape remain poorly understood. Here, we show that the phage homing endonuclease SegB facilitates immune evasion by promoting the segmental amplification of anti-defense loci. The antiphage defense Septu inhibits phage T6 replication by cleaving the variable loop of tRNATyr. We show that SegB enables immune evasion by amplifying a genomic segment that contains the full-length tRNATyr gene. This repeat expansion increases tRNATyr expression, allowing the phage to overcome Septu immunity. Remarkably, SegB also mediates in trans amplification of distinct anti-defense genes that counteract OLD and toxin-antitoxin ToxIN defense systems. Collectively, our findings demonstrate that SegB-mediated segmental amplification represents a versatile mechanism by which phages rapidly adapt to and circumvent diverse bacterial antiphage defenses.
2026-02-05 | GSE303005 | GEO
Project description:Bacteriophages must overcome diverse bacterial immune systems, yet the molecular principles enabling such escape remain poorly understood. Here, we show that the phage homing endonuclease SegB facilitates immune evasion by promoting the segmental amplification of anti-defense loci. The antiphage defense Septu inhibits phage T6 replication by cleaving the variable loop of tRNATyr. We show that SegB enables immune evasion by amplifying a genomic segment that contains the full-length tRNATyr gene. This repeat expansion increases tRNATyr expression, allowing the phage to overcome Septu immunity. Remarkably, SegB also mediates in trans amplification of distinct anti-defense genes that counteract OLD and toxin-antitoxin ToxIN defense systems. Collectively, our findings demonstrate that SegB-mediated segmental amplification represents a versatile mechanism by which phages rapidly adapt to and circumvent diverse bacterial antiphage defenses.
2026-02-05 | GSE315621 | GEO