Ontology highlight
ABSTRACT:
PROVIDER: PRJNA966776 | ENA |
REPOSITORIES: ENA
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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
Project description:Hypervirulent Klebsiella pneumoniae (hvKp) is a significant pathogen causing severe community-acquired infections, characterized by the presence of a virulence plasmid. The plasmid-encoded regulator of mucoid phenotype A (RmpA) activates the expression of capsule genes, resulting in a hypermucoviscosity phenotype strongly associated with increased virulence. RmpA features a LuxR DNA-binding domain and a signaling-responsive domain, typical of proteins that regulate multiple biological processes. However, the comprehensive regulatory mechanisms of RmpA in hvKp remain unclear. Herein, RNA-seq showed that RmpA activates carbohydrate metabolism pathways while repressing those related to DNA replication, ribosome metabolism, and biofilm formation. ChIP-seq further confirmed RmpA’s role as a global regulator that not only enhances capsule production by activating transcripts within the capsule locus, but also upregulates the expression of key genes involved in synthesizing capsule precursors. RmpA regulates the phenotypic switch between hypermucoviscosity and biofilm formation by repressing type III fimbriae genes. In addition, Expression of RmpA in Escherichia coli induced global transcriptional changes, suggesting it functions as a global regulator across species. These findings position RmpA as a central regulator in hvKp, orchestrating metabolic pathways and phenotypic traits essential for virulence.
2025-01-14 | GSE286111 | GEO
Project description:The study aimed to characterize plasmids mediating carbepenem resistance in Klebsiella pneumoniae in Pretoria, South Africa. We analysed 56 K. pneumoniae isolates collected from academic hospital around Pretoria. Based on phenotypic and molecular results of these isolates, 6 representative isolates were chosen for further analysis using long reads sequencing platform. We observed multidrug resistant phenotype in all these isolates, including resistance to aminoglycosides, tetracycline, phenicol, fosfomycin, floroquinolones, and beta-lactams antibiotics. The blaOXA-48/181 and blaNDM-1/7 were manily the plasmid-mediated carbapenemases responsible for carbapenem resistance in the K. pneumoniae isolates in these academic hospitals. These carbapenemase genes were mainly associated with plasmid replicon groups IncF, IncL/M, IncA/C, and IncX3. This study showed plasmid-mediated carbapenemase spread of blaOXA and blaNDM genes mediated by conjugative plasmids in Pretoria hospitals.
2019-10-17 | GSE138949 | GEO
Project description:Elucidating the RamA Regulon in Klebsiella pneumoniae and the transcriptome profiles of multidrug resistant Klebsiella pneumoniae
2017-12-25 | GSE24688 | GEO
Project description:Hypervirulent Klebsiella pneumoniae (hvKp) is a significant pathogen causing severe community-acquired infections, characterized by the presence of a virulence plasmid. The plasmid-encoded regulator of mucoid phenotype A (RmpA) activates the expression of capsule genes, resulting in a hypermucoviscosity phenotype strongly associated with increased virulence. RmpA features a LuxR DNA-binding domain and a signaling-responsive domain, typical of proteins that regulate multiple biological processes. However, the comprehensive regulatory mechanisms of RmpA in hvKp remain unclear. Herein, RNA-seq showed that RmpA activates carbohydrate metabolism pathways while repressing those related to DNA replication, ribosome metabolism, and biofilm formation. ChIP-seq further confirmed RmpA’s role as a global regulator that not only enhances capsule production by activating transcripts within the capsule locus, but also upregulates the expression of key genes involved in synthesizing capsule precursors. RmpA regulates the phenotypic switch between hypermucoviscosity and biofilm formation by repressing type III fimbriae genes. In addition, Expression of RmpA in Escherichia coli induced global transcriptional changes, suggesting it functions as a global regulator across species. These findings position RmpA as a central regulator in hvKp, orchestrating metabolic pathways and phenotypic traits essential for virulence.
2025-01-14 | GSE286114 | GEO
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:Mosaic resistance and virulence plasmid in Klebsiella pneumoniae IE
| PRJEB89810 | ENA
Project description:Klebsiella pneumoniae is a prominent human pathogen that has developed resistance to multiple antibiotics. While the roles of capsules and siderophores are well established, the identification of additional virulence determinants remains limited. In this study, we hypothesize that the two-component system response regulator CpxR is integral to the regulation of K. pneumoniae virulence via control of specific virulence-associated genes. Deletion of the cpxR gene resulted in reduced serum resistance and attenuated virulence in both Galleria mellonella larvae and murine infection models compared to the wild-type strain. To elucidate the repertoire of virulence-associated genes regulated by CpxR, a multidisciplinary workflow was employed, integrating RNA sequencing, Real-Time quantitative PCR, gene knockout strategies, serum resistance assays, and infection experiments utilizing Galleria mellonella. Among the genes identified with significantly diminished expression following cpxR deletion, KPHS_28080 emerged as a novel candidate virulence-associated gene. Deletion of KPHS_28080 impaired serum survival in both the carbapenem-resistant CRKp HS11286 and the hypervirulent hvKp ATCC43816 strains. Furthermore, deletion of KPHS_28080 in hvKp ATCC43816 led to significantly decreased colonization and impaired dissemination to multiple organs in murine models, corresponding with an overall reduction in virulence. The promoter region of KPHS_28080 harbors a conserved CpxR binding motif, which enhances promoter activity and gene transcription upon CpxR binding. Sequence alignment revealed that KPHS_28080 encodes a member of the short-chain dehydrogenase family, and this gene is highly conserved among K. pneumoniae strains. These results elucidate the pivotal role of CpxR in mediating virulence in K. pneumoniae and clarify its regulatory impact on virulence-associated gene expression.
2025-07-10 | GSE300466 | GEO
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