Similar Datasets
Project description:Intestinal colonization by Klebsiella pneumoniae is recognized as a pivotal prerequisite for its systemic dissemination and subsequent invasive infection; however, the metabolic basis and regulatory mechanisms underlying this process remain poorly understood. In this study, we employed transposon insertion sequencing (Tn-seq) to systematically identify metabolic genes associated with intestinal colonization in hypervirulent Klebsiella pneumoniae (hvKp). By integrating high-throughput screening with in vivo phenotypic validation, we identified the global transcriptional regulator DksA as a key factor that markedly enhances hvKp intestinal colonization. Mechanistically, DksA appears to promote colonization by enhancing carbon source metabolism. Combined transcriptomic analyses with homology modeling and molecular dynamics simulations further revealed that DksA induces cascade allosteric remodeling of key RNA polymerase structural domains, thereby enhancing hvKp utilization of common intestinal carbon sources and facilitating intestinal colonization. Collectively, our findings highlight the critical role of transcriptionally regulated metabolic plasticity in hvKp intestinal colonization and provide a theoretical framework and potential targets for developing anti-colonization strategies that exploit pathogen metabolic vulnerabilities.
2026-03-18 | GSE324122 | GEO
Project description:High-resolution single-cell RNA-seq reveals the immune landscape of hvKp-infected lungs
2023-12-26 | GSE220594 | 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:Hypervirulent Klebsiella pneumoniae (HvKP) is an emerging human pathogen causing invasive infection in immune-competent hosts. The hypervirulence is strongly linked to the overproduction of hypermucovisous capsule, but the underlining regulatory mechanism of hypermucoviscosity (HMV) has been elusive, especially at the post-transcriptional level mediated by small RNAs (sRNAs). Using a recently developed RNA interactome profiling approach, we have investigated the Hfq-associated sRNA regulatory network and established the first in vivo RNA-RNA interactome in HvKP. Our data reveal numerous interactions between sRNAs and HMV-related mRNAs, and identify a plethora of sRNA that inhibit or promote HMV. One of the strongest repressors of HMV was ArcZ, a conserved sRNA in the Enterobacteriaceae family. We found that ArcZ is activated by the master regulator of catabolite repression Crp, and down-regulates the expression of mlaA encoding an outer-membrane lipoprotein, leading to decreased HMV and virulence attenuation in mice. ArcZ significantly reduced HMV in several carbapenem-resistant and hypervirulent clinical isolates with diverse genetic background, suggesting it is an antisense RNA inhibitor of HMV with therapeutic potential. In summary, our work provides a comprehensive map of the RNA-RNA interaction network of HvKP and identifies ArcZ as a conserved repressor of HMV, providing novel insights into the mechanisms of posttranscriptional regulations of virulence.
2024-07-17 | GSE260738 | GEO
Project description:Hypervirulent Klebsiella pneumoniae (hvKp) causes invasive infections and severe systemic inflammation. In this study, outer membrane vesicles (OMVs) derived from clinically isolated hvKp and classical K. pneumoniae (cKp) strains were characterized using an integrated proteogenomic workflow combining whole-genome sequencing and label-free LC–MS/MS proteomics. The dataset includes quantitative proteomic profiles of OMVs and whole-cell lysates together with strain-specific protein annotations for comparative analyses of OMVs cargo composition, functional annotation, and pathogenicity.
2026-07-22 | PXD045083 | Pride
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:Phage-derived depolymerases represent a promising antibiotic alternative for treating Klebsiella pneumoniae infections. Depolymerases can increase the sensitivity of bacteria to the host immune system and complement-mediated killing by specifically degrading capsular polysaccharides (CPS). However, the impact of depolymerases on bacterial biofilm formation remains unclear. This study found that depolymerase treatment significantly enhances the biofilm formation capability of hypervirulent K. pneumoniae (hvKp) strains, which inherently exhibit relatively weak biofilm formation due to their thick capsular polysaccharide (CPS) layers. Further investigation revealed that depolymerase-mediated CPS degradation relieved its repression on the type 3 fimbriae gene cluster mrkABCDF, thereby promoting biofilm formation. In vivo experiments in mice also showed that CPS can inhibit virulence functions associated with type 3 fimbriae. Furthermore, we found that CPS-mediated biofilm inhibition appears to be a common phenomenon among hvKp strains. In summary, by elucidating the dual role of depolymerase in modulating both virulence and biofilm in hvKp, our work reveals a potential interaction between CPS and type 3 fimbriae, providing deeper insights into the pathogenicity of this clinically important bacterium.
2026-06-28 | PXD080233 | Pride