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ABSTRACT: Complete Genome Sequence of two Klebsiella pneumoniae phages isolated as part of an international effort

PROVIDER: PRJNA555313 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR9705648.fastq.gz	Fastqsanger.gz
	SRR9705649.fastq.gz	Fastqsanger.gz

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The component parts of bacteriophage virions accurately defined by a new machine-learning approach built on evolutionary features.

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

Rapid design of bacteriophage cocktails to suppress the burden and virulence of gut-resident carbapenem-resistant Klebsiella pneumoniae

Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.

2024-10-01 | GSE272297 | GEO

null

Project description:Complete genome of Sequences of two Klebsiella pneumoniae Phages from Dakar, Senegal.

| PRJEB68306 | ENA

Gene expression in Klebsiella pneumoniae

Project description:Elucidating the RamA Regulon in Klebsiella pneumoniae and the transcriptome profiles of multidrug resistant Klebsiella pneumoniae

2017-12-25 | GSE24688 | GEO

Different proteome studies of Klebsiella pneumoniae isolates under common single carbon source treatments

Project description:Klebsiella pneumoniae is a gram-negative bacterium that can cause lung disease in humans. Meanwhile, the contamination situation of Klebsiella pneumoniae in aquaculture environment is critical. In this study, we determined for the first time the growth of Klebsiella pneumoniae isolated from common edible aquatic products in different carbon sources.

2023-11-13 | PXD046917 |

Different secretome and proteome studies of Klebsiella pneumoniae isolates under common single carbon source treatments

2023-11-13 | PXD046919 |

Host Immune Response to Clinical Hypervirulent Klebsiella pneumoniae Pulmonary Infections via Transcriptome Analysis

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

In vivo single cell transcriptomics reveals Klebsiella pneumoniae-governed polarization of ontogenetically distinct macrophage lineages by targeting an evolutionary conserved type I IFN-IL10-STAT6 axis to promote infection.

Project description:Mice were infected with Klebsiella pneumoniae and interstitial and alveolar macrophages isolated and subjected to single cell RNA sequencing to investigate the transcriptomes of Klebseilla-associated and uninfected bystander cells.

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KPHS_28080 Emerges as a Novel Virulence Factor in Klebsiella pneumoniae through CpxR-Dependent Transcriptional Activation

Project description:Klebsiella pneumoniae is an important human pathogen, causing various infections. Apart from traditional virulence factors, there remains a significant gap in the discovery and research of new chromosomal virulence factors. CpxR is a two-component system (TCS) response regulator, but its impact on the virulence of Klebsiella pneumoniae have not been conclusively determined. For the effect of CpxR on K. pneumoniae virulence, the cpxR deletion(ΔcpxR) strain exhibited reduced serum resistance and attenuated pathogenicity in both Galleria mellonella larvae and mouse infection models compared to the wild-type strain. To identify CpxR-regulated virulence genes, RNA-seq analysis was conducted, followed by deletion of transcription downregulated genes in the ΔcpxR strain. Through serum resistance assays and Galleria mellonella infection experiments, a novel potential virulence factor, KPHS_28080, was identified. Deletion of KPHS_28080 impaired serum survival and proliferation in carbapenem-resistant strains HS11286 and hypervirulent strain ATCC 43816. Furthermore, the ATCC 43816 ΔKPHS_28080 strain showed significantly reduced colonization, proliferation, and multi-organ dissemination capacity in mice, accompanied by diminished pathogenicity. The KPHS_28080 promoter contains a conserved CpxR binding motif, where CpxR binding enhances promoter activity and elevates gene transcription. Sequence alignment revealed that KPHS_28080 is widely conserved across Klebsiella pneumoniae strains, establishing it as a novel chromosome-encoded virulence factor. These results provide a new insight into the CpxR regulation of K. pneumoniae virulence and chromosomal virulence factors.

2025-07-10 | GSE300466 | GEO

Verfication of immunogenic nature by microarray screening

Project description:Screening of 14 novel proteins derived from Klebsiella pneumoniae MGH 78578 identified prior via screening of cDNA libraries. The full-length proteins were attached using a specific HaloTag to their corresponding ligand surface, HaloLink. Screening was performed using two different polyclonal antibodies to Klebsiella pneumoniae (Acris AP00792PU-N and Abcam ab20947) and detection achieved by Goat polyclonal to rabbit IgG conjugated with Chromeo-546 (Abcam ab60317). In order to assess their potential immungenic nature and rank the proteins investigated, comparative analysis using already described antigens from K. pneumoniae were used in the assay.

2014-02-02 | GSE52538 | GEO

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