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Gabija restricts phage circularization and DNA replication.

Anti-bacteriophage systems such as restriction-modification and CRISPR-Cas have DNA substrate specificity mechanisms that enable the identification of invaders. How Gabija, a highly prevalent nuclease-helicase antiphage system, limits phage replication while executing self- vs. non-self-discrimination remains unknown. Here, we show that phage-encoded DNA end-binding proteins that antagonize host RecBCD sensitize phages to Gabija. When targeting a temperate lambda-like phage in Pseudomonas aeruginosa, Gabija prevents phage genome circularization and subsequent replication. DNA end-binding complexes, including a phage exonuclease and a single-stranded DNA (ssDNA)-annealing protein or GamMu dimers that prevent loading of the host repair complex RecBCD, are necessary and sufficient to license phage and plasmid sensitivity to Gabija. Mutant escape phages lacking these DNA end-binding proteins become protected from Gabija by RecBCD translocation activities. RecBCD activity on the bacterial genome, presumably whenever it is linearized, also prevents Gabija from targeting self-DNA. Therefore, we propose that Gabija antagonizes the circularization and replication of linear DNA devoid of RecBCD as a mechanism to identify and antagonize foreign invaders.

DNA Replication

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

[Intercellular information transfer in the process of immunogenesis. VI. The induction of antiphage antibody synthesis in the cells of rat transplantable lymphosarcoma under the influence of splenic RNA from rats and mice immunized with phage T2].

It has been proved that nuclear and cytoplasmic RNAs, isolated from spleens of T2 phage immunized rats and mice, can induce T2 phage antibodies in cells of the transplantable rat lymphosarcoma. With the nuclear RNA from rat spleens, the effect is persisting in a number of subsequent cell generations. The data presented are principally in accord with results of the authors' previous studies in which lymphosarcoma cells were treated with RNA extracted from spleens of rat immunized with sheep red cells. These results well compare with the authors' earlier advanced hypothesis suggesting a possible involvement of RNA in deblockation of genes responsible for the synthesis of the antibodies in question.

Animals

Why do bacteria accumulate antiphage defence systems?

While it is well established that bacterial genomes encode multiple and diverse antiphage systems, the reasons for their co-occurrence and their heterogeneous distribution remain debated. This review examines why bacteria accumulate antiphage systems and how this influences phage-bacteria interactions, particularly in the context of phage therapy. Two main hypotheses may explain this phenomenon: (i) the pan-immunity hypothesis, which suggests that defence system accumulation provides protection against phage predation at the community level, and (ii) mobile genetic element (MGE) competition, where defence systems primarily protect intra-bacterial MGEs against other ones rather than the bacterial host itself. The ecological context also influences the distribution of antiphage systems, with defencee accumulation shaping phage-bacteria interactions in diverse communities but playing a lesser role at the species level, potentially explaining why multiple defences do not strongly limit phage host range in therapeutic settings. Finally, we address the challenges in understanding the drivers shaping the distribution of defence systems across bacterial genomes (expressions, costs, etc.) and their implications for elucidating the ecological role of defence systems and optimizing phage therapy strategies.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.

Bacteria

Indication of antigens and antibodies using the reaction of compound immune adsorption and reactivation of the phage.

A method of determining antibodies by their adsorption on large-pore or surface immunosorbents with subsequent treatment of the carrier with anti-immunoglobulin serum and antiphage serum isologous to the antibodies and then with the bacteriophage has been presented. The adsorbed virions are split off by means of papain-induced hydrolysis of the antibody complex. The antigens are determined by the reaction of phage fixing inhibition. The method permits to determine small amounts of antibodies to proteins, haptenes and cells with objective calculation of results.

Antibodies, Bacterial

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

[Studies on the relationship of temperent phages and bacteriocines of streptococcus faecium (author's transl)].

Two bacteriocins (enterocin E1A and E1B) as well as a complete bacteriophage (PE1) were produced by Streptococcus faecium strain E1. Although the phage could be demonstrated by electron microscopy it was not possible to observe phages or phage-like particles in the purified preparation of the large enterocin E1B. Phage PE1 had a much smaller activity spectrum than that of enterocin E1A and E1B, inhibiting only one strain of Streptococcus faecium and one strain of Streptococcus salivarius. The enterocins were not neutralized by antiphage sera, thereby suggesting that the enterocins and the phage are chemically unrelated.

Animals

[Lysogenic clones of wild-type plague bacteria and characteristics of the phages produced by them].

Comparative population analysis of 3 lysogenic clones of plague bacteria of wild type by lysogenic properties demonstrated that they failed to show any difference from one another by immunity to homolgous and heterologous phages, but differed by the number of cells capable of producing the phage spontaneously. Lysogenic properties were transmitted by heredity both after the ten-fold passage in the presence of a homologous antiphage serum and after a 10-fold colning. Phages produced by the wild lysogenic clones of plague bacteria were capable of provoking lysogenization of bacteria sensitive to it, they were serologically affiliated and differed by the range of action on plaque and pseudotuberculosis bacteria sensitive to it.

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