Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1136040 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29836910_1.fastq.gz | Fastqsanger.gz | |||
| SRR29836910_2.fastq.gz | Fastqsanger.gz | |||
| SRR29836911_1.fastq.gz | Fastqsanger.gz | |||
| SRR29836911_2.fastq.gz | Fastqsanger.gz | |||
| SRR29836912_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 44 |
Similar Datasets
Project description:Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is secreted by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth phase-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of Escherichia coli (E. coli), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane and bacterial death notably contribute to ATP release. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analysed using a transformed E. coli bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.
2024-07-16 | GSE272296 | GEO
Project description:Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is released by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of Escherichia coli (E. coli), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane notably contributes to ATP release and is associated with bacterial death. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analyzed using a transformed E. coli bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.
| S-EPMC11335348 | biostudies-literature
Project description:This study examined global proteomic changes in blood plasma from non-Hispanic White and African American sepsis patients with primary intra-abdominal infection using LC-MS/MS on a Q-Exactive HF. Proteins were quantified in the LC-MS/MS experiments using Tandem Mass Tags 16-plex (TMTpro).
2022-09-13 | PXD030476 | Pride
Project description:The CS and CLP murine models of intra-abdominal sepsis have unique transcriptomic respones 2 hrs, 1 and 3 days after sepsis
2014-02-21 | GSE55238 | GEO
Project description:The CS and CLP murine models of intra-abdominal sepsis have unique transcriptomic respones 2 hrs, 1 and 3 days after sepsis We used mouse microarrays to detail the molecular profile of the events that occur following infection in two different sepsis models Infection protocol: Used the Cecal Ligation and Puncture (CLP) model and Cecal Slurry (CS) method in young mice.
2014-02-21 | E-GEOD-55238 | biostudies-arrayexpress
Project description:Sepsis is an uncontrolled, systemic response to infection with life-threatening consequences. Our understanding of the pathogenesis of sepsis across organs of the body is rudimentary. Here, using mouse models of sepsis, we generate a dynamic, organism-wide map of the pathogenesis of the disease, revealing the spatiotemporal patterns of well-known and previously unrecognized effects of sepsis on the body. By combining functional perturbations with organism-wide profiling, we discover two interorgan mechanisms that are key to the pathophysiology of sepsis. First, we find that a hierarchical cytokine circuit arising from the pairwise effects of TNF plus IL-18, IFN-γ, or IL-1β suffices to explain a large fraction of the molecular effects of sepsis on the body. Moreover, the effects of these three cytokine pairs on the abundance of nearly two hundred cell types across nine organ types recapitulate half of all the cellular effects of sepsis. Second, we uncover an interorgan pathway whereby a gut-derived, secreted phospholipase, Pla2g5, mediates hemolysis in the blood circulation and contributes to multi-organ failure during sepsis. Thus, a simplifying principle in the systemic behavior of the cytokine network and a lipase misdirected from gut to blood provide fundamental insights to help build a unifying mechanistic framework for the pathophysiological effects of sepsis on the organ systems of the body.
2024-01-11 | GSE253061 | GEO
Project description:Despite decades of research, sepsis remains one of the most urgent unmet medical needs. Clinical trials in sepsis have mainly focused on targeting the inflammatory pathway, however, recent data indicate that sepsis should also be seen as a metabolic disease. Targeting metabolic dysregulations that take place in sepsis might uncover novel therapeutic opportunities to treat human sepsis patients. The role of PPARα in liver dysfunction during sepsis has recently been described, and restoring PPARα signaling proves to be successful in murine sepsis. To find out whether this therapy might also be helpful in human sepsis patients, we analyzed metabolic perturbations in liver of a porcine fecal peritonitis model. Resuscitation with fluids, antimicrobial therapy and abdominal drainage were applied to the pigs in order to mimic human clinical care. By using RNA-seq, we detected problems with PPARα signaling in the livers of septic pigs and reduced PPARα levels correlated well with disease severity. As PPARα regulates the expression of many genes involved in FA oxidation, reduced expression of these target genes concomitant with increased FFAs in plasma and ectopic lipid deposition in the liver was observed. The results obtained in pigs are in agreement with earlier observations in mice and support the potential of targeting defective PPARα signaling in the clinic.
2022-11-28 | GSE218636 | GEO
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.
2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress
Project description:To identify genes that are regulated by KLF5 during vascular smooth muscle cell mitochondrial mophology, redox and ATP, we performed RNA expression profiling using microarray analyses of AAA and normal abdominal aortas from WT (control) and smcKlf5−/− mice. The experiments showed that mitochondrial mophology-, redox- and ATP-related gene expressions markedly differed between AAA and normal aortic tissues.
2020-09-09 | GSE148841 | GEO
Project description:Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. Experiment Overall Design: Exploratory studies were conducted using spleens from septic patients and from mice with abdominal sepsis. Seven patients with sepsis after injury were identified retrospectively and compared with six injured patients. C57BL/6 male mice were subjected to cecal ligation and puncture, or to IP lipopolysaccharide. Control mice had sham laparotomy or injection of IP saline, respectively. A sepsis classification model was created and tested on blood samples from septic mice.
2008-06-14 | E-GEOD-5663 | biostudies-arrayexpress