Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25936542_1.fastq.gz | Fastqsanger.gz | |||
| SRR25936542_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Antibiotic resistance is one of the most pressing threats to human health, yet recent work highlights how loss of resistance may also drive pathogenesis in some bacteria. In two recent studies, we found that in vitro beta-lactam antibiotic and nutrient stresses faced during infection selected for the genetic inactivation of the Pseudomonas aeruginosa (Pa) antibiotic efflux pump mexEFoprN. Unexpectedly, efflux pump mutations increased Pa virulence during infection; however, neither the prevalence of efflux pump inactivating mutations in real human infections, nor the mechanisms driving increased virulence of efflux pump mutants were known. We hypothesized that human infection would select for efflux pump mutations that drive increased virulence in Pa clinical isolates. Using genome sequencing of hundreds of Pa clinical isolates, we show that mexEFoprN efflux pump inactivating mutations are enriched in Pa cystic fibrosis isolates relative to Pa intensive care unit clinical isolates. Combining RNA-seq, metabolomics, genetic approaches, and infection models we show that efflux pump mutants increase expression of two key Pa virulence factors, elastase and rhamnolipids, which increased Pa virulence and lung damage during both acute and chronic infections. We show that increased virulence factor production was driven by increased Pseudomonas quinolone signal levels, and this mechanism of increased virulence held true in both a representative ICU clinical isolate and the notorious CF Pa Liverpool epidemic strain. Together, our findings suggest that mutations inactivating antibiotic resistance mechanisms could increase patient mortality and morbidity.
2024-11-12 | MSV000096391 | MassIVE
Project description:Segment 3 of influenza A virus contains a second open reading frame accessed via robosomal frameshifting. The frameshift product, PA-Z, comprises the endonuclease domain of viral PA protein with C-terminal demain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model.
2012-07-12 | GSE38112 | GEO
Project description:PA-X is a small accessory protein that modulates the virulence of various influenza A virus both in mammals and birds. However, the specific role of PA-X in the pathogenesis of highly pathogenic avian influenza virus (HPAIV) H7N9 subtype in mammals and avian species is largely unknown. By functional analysis, we want to investigate critical amino acids that contribute to the host shutoff ability of the PA-X protein of the H7N9 virus in 293T cells
2024-05-02 | GSE204790 | GEO
Project description:Inorganic phosphate (Pi) is a central nutrient and signal molecule for bacteria. Pi limitation was shown to increase the virulence of a number of phylogenetically diverse pathogenic bacteria with different in lifestyles. Hypophosphatemia enhances the risk of death in patients due to general bacteremia and was observed after the surgical injury in humans and animals. Phosphate therapy, or the reduction of bacterial virulence by the administration of Pi or phosphate-containing compounds, is a promising anti-infective therapy approach that will not cause cytotoxicity nor the emergence of antibiotic-resistant strains. The proof of concept of phosphate therapy has been obtained using primarily Pseudomonas aeruginosa (PA) as a model. However, a detailed understanding of Pi-induced changes at protein levels is missing. Using pyocyanin production as proxy, we show that the Pi-mediated induction of virulence is a highly cooperative process that occurs between 0.2 to 0.6 mM Pi. We present a proteomics study of PA grown in minimal medium supplemented with either 0.2 or 1 mM Pi and rich medium. About half of the predicted PA proteins could be quantified. Among the 1,471 dysregulated proteins comparing growth in 0.2 mM to 1 mM Pi, 1100 were depleted under Pi-deficient conditions. Most of these proteins are involved in general and energy metabolism, different biosynthetic and catabolic routes, or transport. Pi depletion caused accumulation of proteins that belong to all major families of virulence factor categories, including pyocyanin synthesis, secretion systems, quorum sensing, chemosensory signaling and the secretion of proteases, phospholipases and phosphatases.
2022-11-02 | PXD033250 | Pride
Project description:Segment 3 of influenza A virus contains a second open reading frame accessed via robosomal frameshifting. The frameshift product, PA-Z, comprises the endonuclease domain of viral PA protein with C-terminal demain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model. The effect of PA-X deltions were examined using 2 separate mutant influenza viruses (1918-FS/1918-PCT1) and the results compared to wild-type 1918 influenza virus. Balb/c mice were infected and samples harvested at days 3, 5 and 8 days. Four animals/condition were used. Gene expression levels from infected animals were compared to mock animals.
2012-07-11 | E-GEOD-38112 | biostudies-arrayexpress
Project description:Accumulation of lipids in the tumor microenvironment (TME) is a feature of several solid tumors and increased palmitate (PA) availability fosters tumor progression and metastases. The intrinsic effects of PA on cancer cells are well understood, but its role in modulating CD8+ T cells (CTL) functional performances remains elusive. Here, we found that PA alters the mitochondrial metabolism of CTL and prevents their effector functions in an irreversible manner, resulting in impaired antitumoral immunity. Mechanistically, PA-induced mitochondrial blocking demotes histone acetylation and chromatin accessibility and decreases the transcription of genes promoting DNA replication and production of effector molecule production. We identified the metabolic enzyme Sphingosine Kinase 2 (SPHK2) as a molecular target of PA in establishing CTL dysfunction. Consistently, pharmacological inhibition of SPHK2 restored CTL mitochondrial fitness, effector functions and anti-tumor potential. Thus, we reveal that PA fosters tumor progression by impairing CTL antitumor immunity and highlight the therapeutic potential of inhibiting SPHK2 activity to optimize T cellfunctionality.
2025-10-06 | GSE251812 | GEO
Project description:Pseudomonas aeruginosa (PA) is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How PA, in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate the changes in gene expression seen when PA is challenged with the high levels of OS present in chronic wounds. We used a biofilm-forming PA strain isolated from the chronic wounds of our murine model (RPA) and performed a qPCR to obtain gene expression patterns as RPA developed a biofilm in vitro in the presence of high levels of OS, and then compared the findings in vivo, in our mouse model of chronic wounds. We found that the planktonic bacteria under OS conditions overex-pressed quorum sensing genes that are important for the bacteria to communicate with each other, antioxidant stress genes important to reduce OS in the microenvironment for survival, biofilm formation genes and virulence genes. Additionally, we performed RNAseq in vivo and identified the activation of novel genes/pathways of the Type VI Secretion System (T6SS) involved in RPA pathogenicity. In conclusion, RPA appears to survive the high OS microenvironment in chronic wounds and colonizes these wounds by turning on virulence, biofilm-forming and survival genes. These findings reveal pathways that may be promising targets for new therapies aimed at dis-rupting PA-containing biofilms immediately after debridement to facilitate the treatment of chronic human wounds.
2024-05-26 | GSE267862 | GEO
Project description:Pseudomonas aeruginosa (Pa) is one of the main causative agents of nosocomial infections and the spread of multidrug-resistant strains is rising. The outer membrane composition of Pa restricts antibiotic entry and determines virulence. For efficient outer membrane protein biogenesis, the BAM complex and chaperones like Skp and SurA are crucial. Deletion mutants of bamB, bamC and the skp homolog hlpA as well as a conditional mutant of surA were investigated. The most profound effects were associated with a lack of SurA, characterized by increased membrane permeability, enhanced sensitivity to antibiotic treatment and attenuation of virulence in a Galleria mellonella infection model. Strikingly, the conditional deletion of surA in a multidrug-resistant bloodstream isolate re-sensitized the strain to antibiotic treatment. Mass spectrometry revealed striking alterations in the outer membrane composition. Thus, SurA of Pa is important for the insertion of many porins, type V secretion systems, TonB-dependent receptors, proteins involved in LPS transport and BAM complex components. Therefore, SurA of Pa serves as a promising target for developing a drug that shows antiinfective activity and sensitizes multidrug-resistant strains to antibiotics.
2019-03-12 | PXD011849 | Pride
Project description:Background. The pathogenesis of influenza A virus subtype H5N1 (hearafter, "H5N1") infection in humans is not completely understood, although hypercytokinemia is thought to play a role. We previously reported that most H5N1 viruses induce high cytokine responses in human macrophages, whereas some H5N1 viruses induce only a low level of cytokine production similar to that induced by seasonal viruses. Methods. To identify the viral molecular determinants for cytokine induction of H5N1 viruses in human macrophages, we generated a series of reassortant viruses between the high cytokine inducer A/Vietnam/UT3028II/03 clone 2 (VN3028IIcl2) and the low inducer A/Indonesia/UT3006/05 (IDN3006), and evaluated cytokine expression in human macrophages. Results. Viruses possessing the acidic polymerase (PA) gene of VN3028IIcl2 exhibited high levels of hypercytokinemia-related cytokine expression in human macrophages, compared with IDN3006, but showed no substantial differences in viral growth in these cells. Further, the PA gene of VN3028IIcl2 conferred enhanced virulence in mice. Conclusions. These results demonstrate that the PA gene of VN3028IIcl2 affects cytokine production in human macrophages and virulence in mice. These findings provide new insights into the cytokine-mediated pathogenesis of H5N1 infection in humans.
2012-09-30 | GSE40711 | GEO