Similar Datasets
Project description:Carbapenems are last-line β-lactam antibiotics for multidrug-resistant Gram-negative infections, yet the adaptive routes by which Enterobacterales survive carbapenem stress remain incompletely understood. Here we show that prolonged subinhibitory meropenem exposure promotes O-antigen loss in Klebsiella pneumoniae, predominantly via insertion sequence-mediated disruption of O-antigen biosynthesis genes, thereby enhancing carbapenem resistance. O-antigen deficiency is accompanied by envelope-associated redox remodeling and reprogramming of central metabolism, mitigating meropenem-induced reactive oxygen species (ROS) accumulation and oxidative killing. This adaptation also conferred collateral sensitivity to aminoglycosides, associated with increased outer-membrane electronegativity and altered porin expression that may promote aminoglycoside uptake. Analysis of public genomes further revealed O-antigen locus disruptions in subsets of K. pneumoniae and Escherichia coli isolates. Together, our findings establish O-antigen deficiency as a surface-remodeling adaptation that enhances carbapenem resistance through coordinated metabolic and redox reprogramming, while exposing an aminoglycoside vulnerability that warrants further evaluation.
2025-09-16 | GSE307523 | GEO
Project description:O-antigen Loss Modulates Meropenem Resistance in Klebsiella pneumoniae Through Metabolic and Redox Reprogramming
| PRJNA1321917 | ENA
Project description:Meropenem is one of the main antibiotics used in the clinical treatment of CRKP. This study demonstrated that some important metabolic changes occurred in Meropenem-induced CRKP-OMVs, The OMVs proteome expression profile indicates increased secretion of stress proteins released from Meropenem-induced Klebsiella pneumoniae. Furthermore, this is the first study to discuss the protein-protein interaction network of the OMVs released by CRKP, especially under antibiotic stress.
2023-12-05 | PXD047553 |
Project description:Antimicrobial resistance (AMR) arises from complex genetic and regulatory changes, including single mutations, gene acquisitions or cumulative effects. Advancements in genomics and proteomics facilitate more comprehensive understanding of the mechanisms behind antimicrobial resistance. In this study, 74 clinically obtained Klebsiella pneumoniae isolates with increased meropenem and/or imipenem MICs were characterized by broth microdilution and PCR to check for the presence of carbapenemase genes. Subsequently, a representative subset of 15 isolates was selected for whole genome sequencing (WGS) by Illumina and Nanopore sequencing, and proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the mechanisms underlying the differences in carbapenem susceptibility of Klebsiella pneumoniae isolates. Identical techniques were applied to characterize 4 mutants obtained after sequential meropenem exposure. We demonstrated that in clinically obtained isolates, increased copy numbers of blaOXA-48 containing plasmids, combined with OmpK36 loss, contributed to high carbapenem MICs without involvement of OmpK35 or other porins or efflux systems. In the meropenem exposed mutants, increased copy numbers of blaCTX-M-15 or blaOXA-48 containing plasmids, combined with OmpK36 loss was demonstrated. The OmpK36 loss resulted from the insertion of IS1 transposable elements or partial deletion of the ompK36 gene. Additionally, we identified two mutations, C59A and C58A, in the DNA coding the copA antisense RNA of IncFII plasmids and multiple mutations of an IncR plasmid, associated with increased plasmid copy numbers. This study demonstrates that by combining WGS and LC-MS/MS, the effect of genomic changes on protein expression related to antibiotic resistance and the mechanisms behind antibiotic resistance can be elucidated.
2025-06-06 | PXD061983 | Pride
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: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:The increasing antibiotic resistance of Klebsiella pneumoniae poses a serious threat to global public health. To investigate the antibiotic resistance mechanism of Klebsiella pneumonia, we performed gene expression profiling analysis using RNA-seq data for clinical isolates of Klebsiella pneumonia, KPN16 and ATCC13883. Our results showed that mutant strain KPN16 is likely to act against the antibiotics through increased increased butanoate metabolism and lipopolysaccharide biosynthesis, and decreased transmembrane transport activity.
2023-04-18 | GSE229867 | GEO
Project description:Effective host defense against infection relies on the tight coordination of immune activation, metabolic adaptation, and redox control, yet how these processes are integrated remains incompletely understood. Here, we identify dipeptidyl peptidase 3 (Dpp3) as a negative regulator of antimicrobial immunity. Dpp3-/- mice exhibit enhanced resistance to Klebsiella pneumoniae infection, with reduced bacterial burden, preserved tissue integrity, and attenuated systemic inflammation. This response is associated with increased phagocytic activity, expansion of germinal centres and plasma cells, and elevated interferon-γ production by T cells. Mechanistically, Dpp3 deficiency leads to reduced Nrf2 protein levels upon stimulation, resulting in heightened ROS accumulation and amplified NF-κB signaling. Integrated metabolomic and transcriptomic analyses of Dpp3-/- immune cells reveal mitochondrial dysfunction and a shift toward biosynthetic and antioxidant-supportive metabolic programs. Collectively, our findings identify Dpp3 as a molecular brake on host defense and uncover a regulatory axis linking redox balance, immunometabolism, and inflammation during infection.
2026-06-09 | GSE320460 | GEO
Project description:<p>Rapid detection of carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) is essential for effective clinical management and surveillance. This study investigated volatile organic compounds (VOCs) as phenotypic biomarkers of carbapenem resistance, with the goal of developing a translationally viable diagnostic metric. Sixteen clinical <em>K. pneumoniae </em>isolates comprising both CRKP and susceptible (CSKP) strains, were cultured for six hours in headspace vials and VOCs extracted using PDMS-coated probes, with and without meropenem. Volatiles were analysed by thermal desorption-gas chromatography-mass spectrometry. Under meropenem stress, CRKP and CSKP exhibited distinct VOC profiles, with two leucine-derived metabolites, 3-methyl-1-butanol (syn. isoamyl alcohol) and 3-methylbutanal (syn. isovaleraldehyde), emerging as key discriminatory features. The ratio of these two metabolites accurately classified resistance phenotype, achieving 100% sensitivity and 94.1% specificity. The ratio also correlated significantly with minimum inhibitory concentration and zone of inhibition values. Stable isotope tracing confirmed their origin from leucine catabolism, and metabolic supplementation experiments suggested a functional role for 3-methyl-1-butanol in promoting growth under antibiotic stress. These findings show that antimicrobial resistance is accompanied by detectable shifts in volatile metabolism and that VOCs can serve as reliable indicators of resistance phenotype. The 3-methyl-1-butanol/3-methylbutanal ratio presents a robust biomarker of meropenem resistance, detectable within six hours of culture growth, and supports the further development of volatilome-based diagnostics for clinical microbiology.</p>
2026-06-09 | MTBLS13539 | MetaboLights