Search PubMedSearch

SEARCH · Search PubMed

Results for “Antiphage defense systems”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

6 recordsLinked to original sources

Small serine recombinases are markers for antiphage defense system discovery.

Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.

Bacteriophages

Plasmids as persistent genetic reservoirs of bacterial defense systems in wastewater treatment.

BACKGROUND: Bacterial antiphage defense systems play essential roles in microbial ecology, yet their dynamics within urban wastewater systems (UWS) remain poorly characterized. RESULTS: In this study, we performed comprehensive metagenomic and plasmidome analyses on 78 wastewater samples collected during two seasons and four sampling points across UWS from three European countries. We observed a significant reduction in the abundance, diversity, and mobility potential of defense systems during biological treatment. However, these reductions were not directly correlated with changes in microbial abundance. Defense systems were significantly enriched on plasmids, particularly conjugative plasmids, where their gene density was approximately twice as high as on chromosomes and remained relatively stable across compartments. In contrast to chromosomal defense systems, plasmid-borne systems exhibited more frequent co-localization with a wide range of mobile genetic elements (MGEs)-associated genes, thereby facilitating multilayered dissemination networks. Furthermore, we detected a strong correlation between phage abundance and host defense system profiles, indicating ongoing phage-host co-evolutionary dynamics in these environments. CONCLUSIONS: In summary, our results demonstrate that UWS reduce the abundance and diversity of bacterial defense system genes. However, plasmid-associated defense systems can persist through shared mobile genetic reservoirs. These findings underscore the critical role of plasmids in bacterial immunity and provide new insights into defense system dynamics within urban wastewater environments.

Plasmids

Disassembly activates Retron-Septu for antiphage defense.

Retrons are antiphage defense systems that produce multicopy single-stranded DNA (msDNA) and hold promise for genome engineering. However, the mechanisms of defense remain unclear. The Retron-Septu system integrates retron and Septu antiphage defenses. Cryo-electron microscopy structures reveal asymmetric nucleoprotein complexes comprising a reverse transcriptase, msDNA (a hybrid of msdDNA and msrRNA), and two PtuAB copies. msdDNA and msrRNA are essential for assembling this complex, with msrRNA adopting a conserved lariat-like structure that regulates reverse transcription. Notably, the assembled Retron-Septu complex is inactive, with msdDNA occupying the PtuA DNA binding site. Activation occurs upon disassembly, releasing PtuAB, which degrades single-stranded DNA to restrict phage replication. This "arrest-and-release" mechanism underscores the dynamic regulatory roles of msDNA, advancing our understanding of antiphage defense strategies.

Cryoelectron Microscopy

Short-term virus-host interactions and functional dynamics in recently deglaciated Antarctic tundra soils.

Long-term chronosequence studies have shown that, as glaciers retreat, newly exposed soils become colonized through primary succession. To determine the key drivers of this process and their vulnerability to climate change, the short-term responses of these pioneering microbial communities also need to be elucidated. Here, we investigated how the taxonomic and functional structure of microbial communities, including viruses, changed over a 7-year period in an Antarctic glacier forefield. Using metagenomics and metatranscriptomics we assessed the influence of both abiotic and biotic factors on these communities. Our results revealed a highly heterogeneous bacteria-dominated microbial community, with Pseudomonas as the most abundant genus, followed by Lysobacter, Devosia, Cellulomonas, and Brevundimonas. This community exhibited the capacity for aerobic anoxygenic phototrophy, carbon and nitrogen fixation, and sulfur cycling, processes vital for survival in nutrient-poor environments. 52 high-quality metagenome-assembled genomes (MAGs) were recovered, representing both transient and cosmopolitan taxa, some of which were able to rapidly respond to environmental changes. A diverse and highly dynamic collection of lytic and temperate viruses was identified across all samples, with high clonal viral genomes typically detected in only one of the eight samples analyzed. Metatranscriptomic analyses confirmed the activity of lytic viruses, while prophage genomes featured much lower expression levels. Prophages appeared to influence host fitness through the expression of genes encoding membrane transporters. Additionally, the abundance of genes linked to antimicrobial compound synthesis and resistance, along with antiphage defense systems, highlights the importance of biotic interactions in driving microbial community succession and shaping short-term responses to environmental fluctuations.

Antarctica

Dental wastewater reveals a hidden reservoir of oral bacteriophage diversity.

Bacteriophages (phages) are being explored as alternatives or complements to antibiotics because of their ability to selectively kill bacterial pathogens. However, phages that infect many oral bacteria remain undiscovered. Here, we discovered that dental wastewater harbors previously underexplored phage diversity. Viral particles concentrated from dental wastewater displayed diverse morphologies, including abundant filamentous phage-like particles. Deep long-read metagenomic sequencing of concentrated viral particles generated 7.4 billion bases of sequence data and yielded 255 medium- to high-quality viral operational taxonomic units (vOTUs), including 46 predicted complete genomes. Comparison with large phage databases revealed that 63 of these 255 vOTUs had no detectable match, indicating that extensive sequencing of dental wastewater substantially expands the number of potential bacteriophages associated with the human oral microbiome. Host prediction linked many vOTUs to oral-associated bacterial taxa, including species with few or no previously reported phages, such as Porphyromonas gingivalis, Tannerella forsythia, and Candidatus Saccharibacteria. Functional annotation identified diverse genes associated with antiphage defense systems within a subset of vOTUs, suggesting that oral phages may contribute to the movement of genes encoding bacterial immune functions within the oral microbiome. Together, these findings expand the known oral phageome and show that dental wastewater contains a largely untapped diversity of phages.IMPORTANCEThe human oral cavity contains a diverse microbial community, but the bacteriophages (phages) that infect many oral bacteria remain poorly characterized. This gap limits our understanding of how phages shape oral microbial communities. Here, we show that dental wastewater is an underexplored source of oral phage diversity. Deep long-read metagenomic sequencing revealed 255 medium- to high-quality phage operational taxonomic units, many of which are not present in existing oral phage databases. These genomes include predicted phages of periodontal disease-associated bacteria and other oral taxa with few or no known phages. Dental wastewater therefore expands the known human oral phageome and reveals candidate phages linked to bacteria associated with oral health and disease.

Bacteriophages

Conservation of antiviral systems across domains of life reveals immune genes in humans.

Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.

Humans