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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↗

[Serological studies of Pseudomonas aeruginosa bacteriophages].

Investigated were 11 phages isolated from lysogenic strains of Pseudomonas aeruginosa. Based on the results of the neutralization test the phages were divided into 3 clearly distinguished groups. The first group embraced phages P28 and C18, the second one--phages 5118, 05, 14, and 141, and the third one--phages 159 and 32. Bacteriophages 10, 12, and 149 produced slightly manifested (23 to 43 per cent) neutralization with P28 and 5118 sera. High-titer and specific antiphage sera were obtained.

Animals↗

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↗

B cell activation via CD40 is required for specific antibody production by antigen-stimulated human B cells.

Costimulatory signals provided by T cells are required for B cells to produce specific antibody (Ab) to T-dependent antigen (Ag) bacteriophage phi x 174. In this study, we demonstrate that if cultured in the presence of anti-CD40, interleukin 10 (IL-10), and Ag, purified B cells can produce antiphage Ab in quantities comparable to those synthesized by B cells cocultured with Ag and T cells. Isotypes produced by B cells in this culture system correspond to those observed in sera of B cell donors. Culture of immunoglobulin (Ig)D- and IgD+ B cells reveals that Ag-induced production of antiphage Ab is restricted to IgD- subset of B cells. In the absence of Ag, anti-CD40/IL-10-stimulated B cells produce only minute amounts of antiphage Ab, indicating that Ag stimulation is indispensable and provides a signal that is synergistic with anti-CD40 and IL-10. Addition of a soluble form of the CD40 ligand (sgp39) to the culture system has a similar effect on specific Ab synthesis as anti-CD40; addition of the soluble construct, CD40 Ig, known to inhibit gp39/CD40 interaction, suppresses in vitro antiphage Ab production by Ag exposed peripheral blood mononuclear cells. Finally, in vivo requirement of gp39/CD40 interaction for specific Ab production was demonstrated by the finding that activated T cells from patients with x-linked hyper IgM syndrome express functionally defective gp39 and respond with depressed Ab titers and fail to switch from IgM to IgG after multiple phage immunizations. These observations illustrate that in vitro and possibly in vivo Ag-specific Ab synthesis requires the presence of Ag and IL-10, and activation signals via CD40.

Antibodies, Viral↗

[Comparative study of the physicochemical and biological properties of Bacillus thuringiensis phages].

Two phages of the polylysogenic Bacillus thuringiensis subsp. galleriae 1-97 culture differ in the morphology of their particles. A comparative study of their antigenic properties has shown the possibility of cross serological reactions of neutralization with antiphagal sera. The results imply that there is an antigenic relationship between these phages. The data indicate that the nucleic acid component of the both phages is DNA. The sensitivity of phage 1-97 A to some physical factors has been studied.

Animals↗

Role in virulence of Shigella flexneri antigens derived from lysogenic conversion.

The virulence of Shigella flexneri var. Y (NTCC 4839), its lysogenic convertants characterized by antigens I, V, and 7, 8, and of a phage-free clone selected by means of antiphage serum was studied. The parent strain was avirulent in the guinea pig eye test and in the "mouse shigellosis" model, but chicken embryo tests indicated the presence of penetrating ability together with defective tissue-growing capacity. The lysogenic convertants failed to regain their virulence to the guinea pig eye and to the mouse, but showed an increased tissue-growing capacity for chicken embryos. The level of virulence of the phage-free derivative equaled that of the parent strain. We concluded that the terminal glucose component of O antigen, even of conversion origin, plays a role as one of the virulence factors in tissue-growing capacity.

Animals↗

Nature of the carrier state of bacteriophage SP-10 in Bacillus subtilis.

Although the association of phage SP-10 with Bacillus subtilis W-23-S(r) persists in heat- and antiserum-resistant form through the spore stage, it is unstable in vegetative cells and frequently terminates in loss of the carried phage or in lysis. On low-tonicity media, the plating efficiency of carrier cells is low. However, high concentrations of succinate or sucrose or a slowed growth rate preserve viability: on 0.48 m succinate-agar, the viable count per optical density unit is the same as that of a noncarrier control culture. Carrier clones retain phage on 0.48 m succinate-agar. At higher succinate levels, many colonies emerge free of phage; at 1 m succinate, all are cured, probably because high succinate inhibits reinfection. Growth of carrier cells in liquid medium with antiphage serum results in rapid curing; events in such cultures with and without succinate were studied quantitatively by tracing the emergence of sensitive cells, the multiplication and induction of carrier cells, and the sensitivity of carrier cells to superinfection with virulent phage. During log phase, 40 to 70% of the carrier cells became sensitive to virulent phage, although the same cells were insensitive during lag and stationary phase. Apparently, fluctuations in repressor levels are responsible. Spontaneous induction of carrier cells followed a qualitatively similar pattern, perhaps in response to changes in level of the same repressor. Production of sensitive segregants by carrier followed a different course, presumably because the repressor does not affect segregation. Many sensitive cells were found two to three divisions after inoculation in antiserum medium. This suggests that each inoculum cell contained one or only a few phage replicons. The data are compatible with the idea that the carrier state in media without antisera is maintained entirely by reinfection and without replication of phage in the latent state. Alternative models which involve replication of latent phage are not ruled out, however.

Bacillus subtilis↗