Ontology highlight
ABSTRACT:
PROVIDER: PRJNA805272 | ENA |
REPOSITORIES: ENA
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Project description:Klebsiella pneumoniae has risen to prominence as a major threat to human health, with hypervirulent and drug-resistant lineages spreading globally. Given their antimicrobial resistant phenotypes, new therapies are required for the treatment of these infections, and bacteriophages (phages) that kill Klebsiella are being identified for use in phage therapy. In order to circumvent the evolution of phage-resistance taking hold the way that drug-resistance has, clear and considered actions are needed in selecting the phages that would be used in therapeutic cocktails. It is known that annotation of phage genomes is poor, potentially obscuring those phages with the most therapeutic potential. Here we show that phages isolated from infrequently sampled environments have features of therapeutic potential and developed a computational tool called STEP3 to understand the evolutionary features that distinguish the component parts of diverse phages, features that proved particularly suitable to detection of virion proteins with only distantly related homologies. These features were integrated into an ensemble framework to achieve a stable and robust prediction performance by STEP3. Proteomics-based analysis of two phages validated the prediction accuracy of STEP3 and revealed the virions contain component parts that include DNA-binding factors, otherwise unrecognizable capsule degradation enzymes and membrane translocation factors.
2021-04-30 | PXD020607 | Pride
Project description:Pseudomonas virus PA5oct has a large, linear, double-stranded DNA genome (286,783 bp) and is related to Escherichia phages 121Q/PBECO 4, Klebsiella phage vB_KleM-RaK2, Klebsiella phage K64-1, and Cronobacter phage vB_CsaM_GAP32. A protein-sharing network analysis highlights the conserved core genes within this clade. Combining hybrid genome sequencing, RNA-Seq and mass spectrometry analyses of its virion proteins allowed us to accurately identify genes and elucidate regulatory elements for this phage (ncRNAs, tRNAs and promoter elements). In total PA5oct encodes 449 CDS of which 93, have been identified as virion-associated based on ESI-MS/MS. The RNA-Seq-based temporal genome organization suggests a gradual take-over by viral transcripts from 21%, 69%, and 93% at 5, 15 and 25 min after infection, respectively . Like many large phages, PA5oct is not organized into contiguous regions of temporal transcription. However, although the temporal regulation of the PA5oct genome expression reveals specific genome clusters expressed in early and late infection, many genes encoding experimentally observed structural proteins surprisingly appear to remain almost untranscribed throughout the infection cycle. Within the host, operons associated with elements of a cryptic Pf1-like prophage are upregulated, as are operons responsible for Psl exopolysaccharide (pslE-J) and periplasmic nitrate reductase (napA-F) production. The characterization described here represents a crucial step towards understanding the genomic complexity as well as molecular diversity of jumbo viruses.
2020-06-04 | GSE130190 | GEO
Project description:Klebsiella pneumoniae lytic phages, genome sequencing and assembly.
| PRJNA739095 | ENA
Project description:The exchange of mobile genomic islands (MGIs) between microorganisms is often mediated by phages. As a consequence, not only phage genes are transferred, but also genes that have no particular function in the phage's lysogenic cycle. If they provide benefits to the phage's host, such genes are referred to as ‘morons’. The present study was aimed at characterizing a set of Enterobacter cloacae, Klebsiella pneumoniae and Escherichia coli isolates with exceptional antibiotic resistance phenotypes from patients in a neonatal ward. Unexpectedly, these analyses unveiled the existence of a novel family of closely related MGIs in Enterobacteriaceae. The respective MGI from E. cloacae was named MIR17-GI. Importantly, our observations show that MIR17-GI-like MGIs harbor genes associated with high-level resistance to cephalosporins. Further, we show that MIR17-GI-like islands are associated with integrated P4-like prophages. This implicates phages in the spread of cephalosporin resistance amongst Enterobacteriaceae. The discovery of a novel family of MGIs spreading ‘cephalosporinase morons’ is of high clinical relevance, because high-level cephalosporin resistance has serious implications for the treatment of patients with Enterobacteriaceal infections.
2018-08-21 | PXD007113 | Pride
Project description:Klebsiella pneumoniae is an arising threat to human health. However, host immune responses in response to this bacterium remain to be elucidated. The goal of this study was to identify the dominant host immune responses associated with Klebsiella pneumoniae pulmonary infection. Pulmonary mRNA profiles of 6-8-weeks-old BALB/c mice infected with/without Klebsiella pneumoniae were generated by deep sequencing using Illumina Novaseq 6000. qRT–PCR validation was performed using SYBR Green assays. Using KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, we identified several immune associated pathways, including complement and coagulation cascades, Toll-like receptor signaling pathway, Rap1 signaling pathway, chemokine signaling pathway, TNF signaling pathway, phagosome and NOD-like receptor signaling pathway, were involved in Klebsiella pneumoniae pulmonary infection. Using ICEPOP (Immune CEll POPulation) analysis, we found that several cell types were involved in the host immune response to Klebsiella pneumoniae pulmonary infection, including dendritic cells, macrophages, monocytes, NK (natural killer) cells, stromal cells. Further, IL-17 chemokines were significantly increased during Klebsiella pneumoniae infection. This study provided evidence for further studying the pathogenic mechanism of Klebsiella pneumoniae pneumonia infection.
2021-03-30 | GSE171048 | GEO
Project description:Bacteriophages (phages) are widespread in Streptococcus pneumoniae, with most strains carrying phage genomes integrated into the chromosome. RNA sequencing was utilised to explore whether phage gene expression could be detected. The pneumococcal reference strain PMEN3 (Spain9V-3), which contained two full-length phages and one partial phage, was grown in broth culture and mitomycin C was added to facilitate phage induction. PMEN3 culture samples were taken at sequential time points and RNA was extracted and sequenced.
2017-02-20 | GSE89200 | GEO
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