Human gut bacteriophages
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA862966 | ENA |
REPOSITORIES: ENA
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Project description:Bacteriophage (phage) therapy is a promising alternative to antibiotics, yet phage-induced immune responses can affect treatment efficacy. However, current methods for assessing phage immunogenicity are limited, hindering the development of safer, more effective therapies. Here, we introduce the Bacteriophage Risk Index (BRI), a novel metric that quantifies phage immunogenic potential based on CpG dinucleotide frequency, motif spacing, and sequence context, key factors influencing Toll-like receptor 9 (TLR9) activation. Applying the BRI to 7,011 phage genomes, we classified them into five risk tiers, revealing substantial immunogenic variability, even among phages targeting the same bacterial host. BRI scores correlated with immune responses in human lung epithelial cells, validating its predictive power. Experimental testing further confirmed this, as exposure of lung epithelial cells to two phages from distinct risk tiers showed that the high-risk phage (Category 4) induced a strong pro-inflammatory response, upregulating CXCL1, CXCL8, IRF7, and TNFAIP3, while the low-risk phage (Category 2) triggered minimal immune activation with limited cytokine expression. These findings confirm that higher BRI scores predict stronger immune responses, providing a robust tool for evaluating phage immunogenicity. By enabling the selection of phages with lower immunogenic potential, the BRI enhances the safety and efficacy of phage therapy while offering a standardized framework for regulatory agencies, clinical researchers, and biologic drug development, with applications extending beyond phage therapy to other immunogenic biologics.
2025-06-16 | GSE293045 | GEO
Project description:Bacteriophage (phage) are viruses that can kill bacteria, but also mediate gene transfer for bacterial evolution. The telomere phages are a curious form using telomere-like structures to replicate their genomes as linear extrachromosomal elements. Here we find that telomere phages are widely distributed in bacteria, being highly prevalent in Klebsiella species. We established a model system to investigate telomere phage biology and find only a small set of phage proteins are expressed in phage-host cells, including a toxin – telocin - that kills other Klebsiella strains. We identify and validate other telocins in the genomes of other, widespread Klebsiella telomere phages. Thus, telomere phages are widespread elements encoding diverse antibacterial weapons and we discuss the prospect of using telocins for precision editing of microbial populations.
2025-05-07 | PXD058604 | Pride
Project description:Phage therapy is a therapeutic approach to treat multidrug resistant infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells derived from a person with cystic fibrosis, we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.
2024-02-19 | GSE255619 | GEO
Project description:Virulent bacteriophages (or phages) are viruses that specifically infect and lyse a bacterial host. When multiple phages co-infect a bacterial host, the extent of lysis, dynamics of bacteria-phage and phage-phage interactions are expected to vary. The objective of this study is to identify the factors influencing the interaction of two virulent phages with different Pseudomonas aeruginosa growth states (planktonic, an infected epithelial cell line, and biofilm) by measuring the bacterial time-kill and individual phage replication kinetics. A single administration of phages effectively reduced P. aeruginosa viability in planktonic conditions and infected human lung cell cultures, but phage-resistant variants subsequently emerged. In static biofilms, the phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only by combining phages and meropenem antibiotic. In contrast, adherent biofilms showed tolerance to phage and/or meropenem, suggesting a spatiotemporal variation in the phage-bacterial interaction. The kinetics of adsorption of each phage to P. aeruginosa during single- or co-administration were comparable. However, the phage with the shorter lysis time depleted bacterial resources early and selected a specific nucleotide polymorphism that conferred a competitive disadvantage and cross-resistance to the second phage. The extent and strength of this phage-phage competition and genetic loci conferring phage resistance, are, however, P. aeruginosa genotype dependent. Nevertheless, adding phages sequentially resulted in their unimpeded replication with no significant increase in bacterial host lysis. These results highlight the interrelatedness of phage-phage competition, phage resistance and specific bacterial growth state (planktonic/biofilm) in shaping the interplay among P. aeruginosa and virulent phages.
2024-07-17 | GSE271537 | GEO
Project description:Ecologically robust gut environment has personalized metabolic responses in Japanese cohort.
| PRJDB13855 | ENA
Project description:Purified phage was used to prevent tumor growth in a mouse model of bacteria aggravated-colorectal cancer. Composite E. coli phage or vehicle control was added to the drinking water of specific pathogen free (SPF) APCmin mice and animals were colonized with E.coli NC101. APCmin mice displayed no overall difference in the number of tumors that formed within the small intestine, however colonization with E. coli NC101 accelerated the growth of tumors resulting in a significant increase in large tumor formation. Importantly, bacteriophage treatment of AIEC colonized APCmin animals significantly reduced E. coli colonization.
2019-03-01 | GSE124123 | GEO
Project description:Bacteria and their viruses (bacteriophages or phages) are in a dynamic arms race that balances predation and resistance, each deploying various strategies, including protein post-translational modifications (PTMs), to achieve dominance. To better understand the role PTMs play in phage infection, we infected Cellulophaga baltica bacteria with three previously characterized phages that represent diverse genomes and infection efficiencies (phi18:1, phi18:4, and phi38:1) to identify proteome-wide and protein-specific trends of PTMs. Approximately double the number of methylated residues on proteins were detected in phage-infected cells (virocells) compared to uninfected cells, and significantly increased frequencies of protein methylation were observed during the early stages of infection. This notable result led to a focus on protein methylation. Phage proteins were detectably methylated in both virocells and free virions, neither of which has been previously reported. Host proteins with known importance to phage infection--including GTPase EF-Tu, chaperone DnaK, and gliding motility proteins--were frequently methylated and/or exhibited methylation patterns in virocells that contrasted those in uninfected cells. Collectively, our results expand on the growing interest of the important role PTMs play in phage infection by demonstrating the dynamic methylation of phage proteins as well as host proteins important to phage infection.
2025-07-11 | MSV000098485 | MassIVE
Project description:High quality pearl millet genomes
| PRJEB71762 | ENA
Project description:This study analysed the temporal transcriptional response of L. lactis UC509.9 undergoing infection with either Tuc2009 or c2, representing phages of two different species (P335 and c2, respectively) of the family Siphoviridae. For the first time, to our knowledge, both DNA microarrays of the host and high resolution tiling arrays of each phage were used provide corresponding data sets of the entire transcriptome at various points post-infection.
2013-06-27 | GSE45655 | GEO