Ontology highlight
ABSTRACT:
PROVIDER: PRJNA767534 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16219306_1.fastq.gz | Fastqsanger.gz | |||
| SRR16219306_2.fastq.gz | Fastqsanger.gz | |||
| SRR16219307.fastq.gz | Fastqsanger.gz | |||
| SRR16219307_1.fastq.gz | Fastqsanger.gz | |||
| SRR16219307_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
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Project description:Genetic Mining of Newly Isolated Salmophages for Phage Therapy
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Project description:Clinical infection caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually increasing and spreading across the world, and phage therapy is a viable application as an alternative to antibiotics. However, additional clinical application is still restricted by the phage resistance. In order to further explore the mechanism of phage resistance, particularly the difference between in vivo and in vitro. Here, we used a mouse intra-abdominal infection (IAI) model to evaluate the antibacterial properties of two lytic phages and further isolated and characterized phage-resistant mutants. Finally, we determined through genomic and transcriptomic analysis that most of the mutation sites in the resistant mutants were located in the capsular polysaccharides gene cluster. However, RM01 and RM12 developed phage resistance by downregulating capsular polysaccharide (CPS) and its transcriptional regulators without any mutations in the CPS gene. In summary, these findings provided further evidence in phage therapy, particularly in addressing the issue of CR-hvKP infections.
2025-09-18 | MTBLS12480 | MetaboLights
Project description:<p>Enzymatic modification of DNA nucleobases can coordinate gene expression, nuclease protection or mutagenesis. We recently discovered a clade of phage-specific cytosine methyltransferase (MT) and 5-methylpyrimidine dioxygenase (5mYOX) enzymes that produce 5-hydroxymethylcytosine (5hmC) as a precursor for enzymatic hypermodifications on viral genomes. Here, we identify phage MT- and 5mYOX- associated glycosyltransferases (GTs) that catalyze linkage of diverse sugars to 5hmC nucleobase substrates. Metavirome mining revealed thousands of new biosynthetic gene clusters containing enzymes with predicted roles in cytosine sugar hypermodification. We developed a platform for high-throughput screening of GT- containing pathways, relying on the E. coli metabolome as a substrate pool. We successfully reconstituted several pathways and isolated diverse sugar modifications appended to cytosine, including mono-, di-, or tri-saccharides comprised of hexoses, N-acetylhexosamines or heptose. These findings expand our knowledge of hypermodifications on nucleic acids and the origins of corresponding sugar-installing enzymes.</p>
2024-08-22 | MTBLS10724 | MetaboLights
Project description:To better understand host/phage interactions and the genetic bases of phage resistance in a model system relevant to potential phage therapy, we isolated several spontaneous mutants of the USA300 S. aureus clinical isolate NRS384 that were resistant to phage K. Six of these had a single missense mutation in the host rpoC gene, which encodes the RNA polymerase beta prime subunit. To examine the hypothesis that the mutations in the host RNA polymerase affect the transcription of phage genes, we performed RNA-seq analysis on total RNA samples collected from NRS384 wild-type (WT) and rpoC G17D mutant cultures infected with phage K, at different time points after infection. Infection of the WT host led to a steady increase of phage transcription relative to the host. Our analysis allowed us to define different early, middle, and late phage genes based on their temporal expression patterns and group them into transcriptional units. Predicted promoter sequences defined by conserved -35, -10, and in some cases extended -10 elements were found upstream of early and middle genes. However, sequences upstream of late genes did not contain clear, complete, canonical promoter sequences, suggesting that factors in addition to host RNA polymerase are required for their regulated expression. Infection of the rpoC G17D mutant host led to a transcriptional pattern that was similar to the WT at early time points. However, beginning at 20 minutes after infection, transcription of late genes (such as phage structural genes and host lysis genes) was severely reduced. Our data indicate that the rpoCG17D mutation prevents the expression of phage late genes, resulting in a failed infection cycle for phage K. In addition to illuminating the global transcriptional landscape of phage K throughout the infection cycle, these studies can inform our investigations into the bases of phage K’s control of its transcriptional program as well as mechanisms of phage resistance.
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Project description:Genomic material isolated from purified phage YerA41 lysate was shown to contain RNA. YerA41 phage lysate was RNase treated to remove phage-external RNA and total RNA was then isolated from the phage preparate using Qiagen Rneasy mini kit. The isolated RNA was sequenced to elucidate its origin. The results suggested that the RNA originated from intact ribosomes of the host bacterium that contaminated the phage lysate.
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Project description:The emergence of carbapenem-resistant Acinetobacter baumannii has been increasingly reported, leading to more challenges in treating its infections. With the development of phage therapy and phage-antibiotic combinations, it is possible to improve the treatment of bacterial infections. In the present study, a vB_AbaP_WU2001 (vWU2001 for short) phage-specific CRAB was isolated and the genome size is 40,792 bp in length. The novel phage vWU2001 belongs to the Autographiviridae family and the order Caudovirales. Shotgun proteomics identified 289 proteins. The broad host range phage vWU2001 displayed a high adsorption rate, short latent period, large burst size and good stability. The phage could reduce preformed biofilms and inhibit biofilm formation. The combination of phage vWU2001 and colistin had significantly higher bacterial growth inhibition activity than that of phage, or colistin alone. The efficacy of the combined treatment was also evaluated in Galleria mellonella. The evaluation of its therapeutic potential revealed that the combination of phage and colistin showed a significantly greater increase in G. mellonella survival and clearance of bacterial number compared to that of phage or colistin alone, indicating that the combination was synergistic against CRAB. The results demonstrated that phage vWU2001 has the potential to be developed as an antibacterial agent.
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Project description:Phage therapy
| PRJEB89930 | ENA
Project description:Microarray based CGH was conducted over a group of 29 strains of S. Enteritidis spanning different epidemiological periods in Uruguay, plus 6 other S. Enteritidis strains isolated from distant geographical regions. We also included 9 Salmonella enterica strains of other serovars isolated in Uruguay. A S. Enteritidis dispensable genome of 233 chromosomal genes and high extent of variation in virulence plasmid was found. Strains isolated before the epidemic show the highest genomic differences as compared with the PT4 reference strain. Comparison with the gene content of other serovars demonstrate extensive horizontal gene transfer between circulating strains beyond serovar definition. Our results show that the epidemic of S Enteritidis in Uruguay was produced by the introduction of strains closely related to PT4, and corroborate the extensive genetic homogeneity among S. Enteritidis isolates worldwide. Phage SE14 emerges as the only specific region for S. Enteritidis. Genetic differences detected in pre-epidemic strains, mainly associated with the absence of phage SE20, suggest that genetic features encoded in this phage may be related to particular epidemiological behavior.
2009-03-03 | E-TABM-603 | biostudies-arrayexpress
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.
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Project description:Phage therapy has garnered significant attention due to the rise of life-threatening multidrug-resistant pathogenic bacteria and the growing awareness of the transfer of resistance genes between pathogens. In light of this, phage therapy applications are now being extended to target plant pathogenic bacteria, like Erwinia amylovora that causes fire blight in apple and pear orchards. Understanding the mechanisms of phage resistance development is crucial for enhancing the effectiveness of phage therapy. Despite the challenges of naturally developing a bacteriophage resistant mutant (BIM) of E. amylovora (without traditional mutagenesis methods), this study successfully created a BIM mutant against the podovirus Ea46-1-A1. The parent strain, E. amylovora D7, and the BIM mutant, B6-2 were compared at the transcriptomic level.
2025-12-09 | GSE291879 | GEO