Ontology highlight
ABSTRACT:
PROVIDER: PRJNA820514 | ENA |
REPOSITORIES: ENA
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Project description:Traditional vaccines are difficult to deploy against the diverse antibiotic-resistant, nosocomial pathogens that cause Hospital Acquired Infections (HAIs). We developed a unique, protein-free vaccine to present antibiotic-resistant HAIs. This vaccine protected mice from invasive infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, multidrug resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Rhizopus delemar, and Candida albicans. Protection persisted even in neutropenic mice infected with A. baumannii or R. delemar. Protection was already apparent after 24 hours and lasted for up to 21 days after a single dose, with a second dose restoring efficacy. Protection persisted without lymphocytes but was abrogated with macrophages depletion. This vaccine induced trained immunity by altering the macrophage epigenetic landscape and the inflammatory response to infection.
2023-08-24 | GSE216061 | GEO
Project description:The emergence of colistin resistance in carbapenem-resistant and extended-spectrum ß-lactamase (ESBL)-producing bacteria is a significant threat to human health, and new treatment strategies are urgently required. Here we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in several polymyxin-resistant, ESBL-producing, carbapenem resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including a ‘next generation’ polymyxin derivative, FADDI-287. To gain additional insight into the potential mechanism of action of PBT2, we analyzed the transcriptome of K. pneumoniae and E. coli in the presence of sub-inhibitory concentrations of PBT2. Treatment with PBT2 was associated with multiple stress responses in both K. pneumoniae and E. coli. Significant changes in the transcription of transition metal ion homeostasis genes were observed in both strains.
2019-06-13 | GSE132637 | GEO
Project description:The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum -lactamase (ESBL)-producing bacteria is a critical threat to human health, and new treatment strategies are urgently required. Here, we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including the less-toxic next-generation polymyxin derivative, FADDI-287. We were unable to select for mutants resistant to PBT2 + FADDI-287 in polymyxin resistant E. coli containing a plasmid-borne mcr-1 gene or K. pneumoniae carrying a chromosomal mgrB mutation. Using a highly invasive K. pneumoniae strain engineered for polymyxin resistance through mgrB mutation, we successfully demonstrated the efficacy of PBT2 + FADDI-287 in vivo for the treatment of Gram-negative sepsis. These data present a new treatment modality to break antibiotic resistance in high priority polymyxin-resistant Gram-negative pathogens.
2020-07-01 | GSE153553 | GEO
Project description:The interactions between Gram-negative respiratory pathogens and the host environment at the site of infection largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional responses of Pseudomonas aeruginosa PA14, Burkholderia thailandensis E264, Klebsiella pneumoniae MGH 78578, and Stenotrophomonas maltophilia K279A exposed to purified pulmonary surfactant (Survanta) through microarrays. This study provides novel insight into the interactions occurring between Gram-negative opportunistic pathogens and the host at an important infection site, and demonstrates the utility of purified lung surfactant preparations for dissecting host-lung pathogen interactions in vitro. The goal of this study was to compare the transcriptional responses of Pseudomonas aeruginosa PA14, Burkholderia thailandensis E264, Klebsiella pneumoniae MGH 78578, and Stenotrophomonas maltophilia K279A exposed to pulmonary surfactant using a custom affymetrix chip designed for their genomes. The goal of this study was to compare the transcriptional responses of Pseudomonas aeruginosa PA14, Burkholderia thailandensis E264, Klebsiella pneumoniae MGH 78578, and Stenotrophomonas maltophilia K279A exposed to pulmonary surfactant using a custom affymetrix chip designed for their genomes.
2018-03-30 | GSE110628 | GEO
Project description:Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in the fight against multidrug-resistant pathogens. Here, we characterize the antibacterial properties and molecular mode of action of the C-terminal fragment of the Medicago truncatula nodule-specific cysteine-rich peptide NCR169 (NCR169C17-38). This peptide exhibits strong bactericidal activity against a broad panel of Gram-positive and Gram-negative pathogens, including members of the ESKAPE group (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli). NCR169C17-38 acted rapidly by permeabilizing bacterial membranes and causing severe morphological damage, outperforming polymyxin B in the rate of membrane disruption. The peptide bound selectively to anionic bacterial lipids such as cardiolipin and displayed remarkable thermal and storage stability. Moreover, NCR169C17-38 effectively inhibited biofilm formation and eradicated pre-formed biofilms of Acinetobacter baumannii even at sub-MBC concentration (3.2 M), a feature not observed for polymyxin B. Transcriptomic analysis of Escherichia coli exposed to sublethal peptide doses revealed a global shutdown of bacterial metabolic and genetic functions, with 450 of 503 differentially expressed genes being downregulated. Strong repression of genes involved in translation, energy production, and cell envelope biosynthesis was accompanied by upregulation of stress- and rescue-related genes linked to membrane repair, ion transport, and oxidative stress responses. Together, these results demonstrate that NCR169C17-38 exerts multifaceted antimicrobial effects - disrupting membranes, binding nucleic acids, and inducing transcriptional collapse - while maintaining its stability and biocompatibility. Together with its previously established antifungal activity and lack of mammalian cytotoxicity, NCR169C17-38 represents a compelling candidate for development as a next-generation antimicrobial agent.
2026-01-21 | GSE312438 | GEO
Project description:The increasing resistence and/or bacterial tolerance to bactericides, such as chlorhexidine, causes worrisome public health problems. Using transcriptomical and microbiological studies, we analysed the molecular mechanisms associated with the adaptation to chlorhexidine in two carbapenemase-producing strains of Klebsiella pneumoniae belonging ST258-KPC3 and ST846-OXA48.
2020-03-21 | GSE147316 | 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:The Translocation and Assembly Module (TAM), composed of TamA and TamB, facilitates the insertion of some β-barrel proteins into the OM of Escherichia coli and Klebsiella pneumoniae, and has also been implicated in lipid homeostasis. However, its role in Pseudomonas aeruginosa remains mostly uncharacterized. To investigate TAM’s function and drug target potential in P. aeruginosa, we generated both single gene knockouts and the tamAB double knockout and isolated outer membrane proteins (OMP) and whole cell lysate (WCP) and run mass spectrometry.
2025-09-16 | PXD067041 | Pride
Project description:Current therapeutic strategies against bacterial infections focus on reduction of pathogen load using antibiotics; however, stimulation of host tolerance to infection in the presence of pathogens might offer an alternative approach. We used computational transcriptomics and Xenopus laevis embryos to discover infection response pathways, identify potential tolerance inducer drugs, and validate their ability to induce broad tolerance. Xenopus exhibits natural tolerance to Acinetobacter baumanii, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae bacteria, whereas Aeromonas hydrophila and Pseudomonas aeruginosa produce lethal infections. Transcriptional profiling led to definition of a 20-gene signature that discriminates between tolerant and susceptible states, as well as identification of a more active tolerance response to gram negative compared to gram positive bacteria. Gene pathways associated with active tolerance in Xenopus, including some involved in metal ion binding and hypoxia, were found to be conserved across species, including mammals, and administration of a metal chelator (deferoxamine) or a HIF-1 agonist (1,4-DPCA) in embryos infected with lethal A. hydrophila increased survival despite high pathogen load. These data demonstrate the value of combining the Xenopus embryo infection model with computational multi-omics analyses for mechanistic discovery and drug repurposing to induce host tolerance to bacterial infections.
2022-06-16 | GSE196424 | GEO