Ontology highlight
ABSTRACT:
PROVIDER: PRJNA777842 | ENA |
REPOSITORIES: ENA
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Project description:With the global increase in the use of carbapenems, several gram-negative bacteria have acquired carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is one of such notorious pathogen that is being widely studied to find novel resistance mechanisms and drug targets. These antibiotic-resistant clinical isolates generally harbor many genetic alterations, and identification of causal mutations will provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance, in which mutated genes that also show significant expression changes among their functionally coupled genes become more likely candidates. For network-based analyses, we developed a genome-scale co-functional network of K. pneumoniae genes, KlebNet (www.inetbio.org/klebnet). Using KlebNet, we could reconstruct functional modules for antibiotic-resistance, and virulence, and retrieved functional association between them. With complementation assays with top candidate genes, we could validate a gene for negative regulation of meropenem resistance and four genes for positive regulation of virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antimicrobial resistance and virulence of human pathogenic bacteria with genomic and transcriptomic profiles from antibiotic-resistant clinical isolates.
2018-06-10 | GSE115539 | GEO
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: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: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:The emergence and spread of polymyxin resistance, especially among Klebsiella pneumoniae isolates threaten the effective management of infections. This study profiled for polymyxin resistance mechanisms and investigated the activity of polymyxins plus vancomycin against carbapenem- and polymyxin-resistant K. pneumoniae.
2023-10-13 | PXD045685 | JPOST Repository
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:This study identified and compared the bacterial diversity and the antimicrobial resistance profile of clinically relevant isolates around a newly developed hospital and university precinct
2024-02-27 | GSE225419 | GEO
Project description:Salmonella Heidelberg is currently the 9th common serovar and has more than twice the average incidence of blood infections in Salmonella. A recent Salmonella Heidelberg outbreak in chicken infected 634 people during 2013-2014, with a hospitalization rate of 38% and an invasive illness rate of 15%. While the company’s history suggested longstanding sanitation issues, the strains’ characteristics which may have contributed to the outbreak are unknown. We hypothesized that the outbreak strains of S. Heidelberg might possess enhanced stress tolerance or virulence capabilities. Consequently, we obtained nine food isolates collected during the outbreak investigation and several reference isolates and tested their tolerance to processing stresses, their ability to form biofilms, and their invasiveness in vitro. We further performed RNA-sequencing on three isolates with varying heat tolerance to determine the mechanism behind our isolates’ enhanced heat tolerance. Ultimately, we determined that (i) many Salmonella Heidelberg isolates associated with a foodborne outbreak have enhanced heat resistance (ii) Salmonella Heidelberg outbreak isolates have enhanced biofilm-forming ability under stressful conditions, compared to the reference strain (iii) exposure to heat stress may also increase Salmonella Heidelberg isolates’ antibiotic resistance and virulence capabilities and (iv) Salmonella Heidelberg outbreak-associated isolates are primed to better survive stress and cause illness. This data helps explain the severity and scope of the outbreak these isolates are associated with and can be used to inform regulatory decisions on Salmonella in poultry and to develop assays to screen isolates for stress tolerance and likelihood of causing severe illness.
2018-09-01 | GSE103418 | GEO
Project description:Virulence is a key trait under selection during host-parasite coevolution. In order to obtain increased fitness, parasites are predicted to increase their ability to circumvent and overcome host immunity. A particular challenge for pathogens are external immune systems, found among various invertebrates. Such external immune systems are chemical defence systems comprised of highly potent antimicrobial compounds released by prospective hosts into the environment. We carried out a coevolution experiment with the entomopathogenic fungus, Beauveria bassiana, and the red flour beetle, Tribolium castaneum, which has a well-documented external immune system. Surprisingly, after just seven transfers of experimental evolution we saw a significant increase in virulence in all B. bassiana. This increase in virulence was mainly the result of the B. bassiana isolates evolving resistance to the external immune defences of the T. castaneum beetles, but not obviously through the increased production of toxins or other harmful substances. Furthermore, transcriptomic analyses of B. bassiana RNA-seq data implicates up-regulation of genes responsible for resistance to oxidative stress underlying the observed resistance. We conclude that external immunity acts as a powerful selective force for virulence evolution, with an increase in virulence being achieved apparently entirely by overcoming these defences, most likely due to elevated oxidative stress resistance.
2017-03-09 | GSE71570 | GEO