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An integrated multi-omics analysis of identiﬁes distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa

ABSTRACT: Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and also cause chronic infections commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we profiled performed to assay for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To find the pivotal transcription factors that are likely involved in host immune defense, we integrally investigated systematic changes in chromatin accessibility and gene expression in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics studies. We discovered that Stat1 and Stat3 were altered in various omics and found similar results in mouse alveolar macrophages. Taken together, these findings indicate that these crucial transcription factors and their downstream signaling molecules play a critical role in the mobilization of host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, as well as provide clear insights and resources for using integrative histological analyses.

ORGANISM(S): Mus musculus

PROVIDER: GSE233206 | GEO | 2023/07/27

REPOSITORIES: GEO

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An integrated multi-omics analysis of identiﬁes distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa

Project description:Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and also cause chronic infections commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we profiled performed to assay for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To find the pivotal transcription factors that are likely involved in host immune defense, we integrally investigated systematic changes in chromatin accessibility and gene expression in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics studies. We discovered that Stat1 and Stat3 were altered in various omics and found similar results in mouse alveolar macrophages. Taken together, these findings indicate that these crucial transcription factors and their downstream signaling molecules play a critical role in the mobilization of host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, as well as provide clear insights and resources for using integrative histological analyses.

2023-07-27 | PXD038001 | Pride

An integrated multi-omics analysis of identiﬁes distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa

2023-07-27 | PXD042381 | Pride

Expression data of Pseudomonas aeruginosa isolates from Cystic Fibrosis patients in Denmark

Project description:CF patients suffer from chronic and recurrent respiratory tract infections which eventually lead to lung failure followed by death. Pseudomonas aeruginosa is one of the major pathogens for CF patients and is the principal cause of mortality and morbidity in CF patients. Once it gets adapted, P. aeruginosa can persist for several decades in the respiratory tracts of CF patients, overcoming host defense mechanisms as well as intensive antibiotic therapies. P. aeruginosa CF strains isolated from different infection stage were selected for RNA extraction and hybridization on Affymetrix microarrays. Two batch of P. aeruginosa CF isolates are chosen : 1) isolates from a group of patients since 1973-2008 as described in ref (PMID: 21518885); 2) isolates from a group of newly infected children as described in ref (PMID: 20406284).

2011-08-05 | E-GEOD-31227 | biostudies-arrayexpress

The Influence of Human Respiratory Epithelia on Pseudomonas aeruginosa Gene Expression

Project description:To gain insights into the initial phases of P. aeruginosa infections and to identify P. aeruginosa genes regulated in response to respiratory epithelia we exposed P. aeruginosa to cultured primary differentiated human airway epithelia. We used a P. aeruginosa strain (PAO1) that causes acute damage to the epithelia and a mutant (PAOSC11) with defects in Type III secretion and in rhamnolipid synthesis. The mutant did not cause rapid damage to epithelia as did the wildtype. Keywords: Pseudomonas aeruginosa and respiratory epithelia

2006-12-19 | GSE4614 | GEO

Expression data of Pseudomonas aeruginosa isolates from Cystic Fibrosis patients in Denmark

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Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches II

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

Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches I

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NeuroLINCS

Project description:<p>The NeuroLINCS Center is part of the NIH Common Fund's Library of Integrated Network-based Cellular Signatures (LINCS) program, which aims to characterize how a variety of human cells, tissues and the entire organism respond to perturbations by drugs and other molecular factors.</p> <p>As Part of the LINCS program, the NeuroLINCS study concentrates on human brain cells, which are far less understood than other cells in the body. Our initial focus is to produce diseased motor neurons from patients by utilizing high-quality induced pluripotent stem cell (iPSC) lines from Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA) patients in addition to unaffected normal healthy controls. Using state-of-the-art OMICS methods (genomics, epigenomics, transcriptomics, and proteomics), we intend to create a wealth of cellular data that is patient-specific in the context of their baseline genetic perturbations and in the presence of other genetic and environmental perturbagens (e.g. endoplasmic reticulum stress). The primary data will be used to build cell signatures that convey the key features that distinguish the state of a cell and determine its behavior. Ultimately, the analysis of these datasets will lead to the identification of a network of unique signatures relevant to each of these motor neuron diseases. The datasets represented in this study are generated from assays interrogating RNA expression (RNA-seq), chromatin accessibility (ATAC-seq) and whole genome sequencing. </p>

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Transcriptomic response of Pseudomonas aeruginosa Z154 planktonic cultures to N-acetylcysteine exposure.

Project description:N-acetylcysteine (NAC) is a mucolytic agent commonly administered together with antibiotics for the treatment of lower respiratory tract infections, which has been demonstrated to exert also an antimicrobial and antibiofilm activity against relevant respiratory pathogens. We analysed the transcriptomic response of P. aeruginosa planktonic cultures to NAC exposure (at concentration achievable by the inhalation route of administration).

2022-05-30 | GSE190946 | GEO

Pseudomonas aeruginosa strain:CLJ3

Project description:Pseudomonas aeruginosa CLJ3 genome sequencing, transcriptomics, and proteomics

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