Project description:Pseudomonas aeruginosa is a common bacteria leading to exacerbations of chronic obstructive pulmonary disease (COPD) patients while this bacteria can be easily eradicated by the immune systems of healthy individuals. Human airway organoids derived from healthy individuals and COPD patients were infected with pseudomonas aeruginosa. This project aims (1) to understand the differences in gene expressions in healthy and COPD airway organoids during stable condition, without infection and (2) to investigate differential pathogenic mechanism (i.e. antimicrobial defense) of pseudomonoas aeruginosa infection in healthy and COPD populations. Three healthy donors and three COPD patients were included in this study and samples were collected with and without pseudomonas aeruginosa infection.
Project description:Gene expression profiles of two Pseudomonas aeruginosa taxonomic outlier clinical isolates, CLJ1 and CLJ3 [CLJ3] Pseudomonas aeruginosa taxonomic outliers emerged recently as infectious for humans, provoking hemorrhagic pneumonia. Those bacteria lack classical type III secretion system, and utilize the pore-forming toxin for infection. Two clones CLJ1 and CLJ3 belonging to these taxonomic outliers have been isolated from the same patient at two different times during hospitalization. P. aeruginosa CLJ3 displays antibiotic resistance phenotype, while CLJ1 is more cytotoxic on epithelial and endothelial cells.
Project description:Gene expression profiles of two Pseudomonas aeruginosa taxonomic outlier clinical isolates, CLJ1 and CLJ3 [CLJ1] Pseudomonas aeruginosa taxonomic outliers emerged recently as infectious for humans, provoking hemorrhagic pneumonia. Those bacteria lack classical type III secretion system, and utilize the pore-forming toxin for infection. Two clones CLJ1 and CLJ3 belonging to these taxonomic outliers have been isolated from the same patient at two different times during hospitalization. P. aeruginosa CLJ3 displays antibiotic resistance phenotype, while CLJ1 is more cytotoxic on epithelial and endothelial cells.
Project description:Pseudomonas aeruginosa airway infection is the primary cause of death in Cystic Fibrosis (CF). During early infection P. aeruginosa produces multiple virulence factors, which cause acute pulmonary disease and are largely regulated by quorum sensing (QS) intercellular signalling networks. Longitudinal clinical studies have observed the loss, through adaptive mutation, of QS and QS-related virulence in late chronic infection. Although the mechanisms are not understood, infection with QS mutants has been linked to a worse outcome for CF patients. By comparing QS-active and QS-inactive P. aeruginosa CF isolates, we have identified novel virulence factors and pathways associated with QS disruption. In particular, we noted factors implicating increased intra-phagocyte survival. Our data present novel targets as candidates for future CF therapies. Some of these targets are already the subject of drug development programmes for the treatment of other bacterial pathogens and may provide cross-over benefit to the CF population. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE25128: Gene expression data from Pseudomonas aeruginosa strains isolated from cystic fibrosis lung infections GSE25129: Comparative genomic hybridisation data from Pseudomonas aeruginosa strains isolated from cystic fibrosis lung infections
Project description:Pseudomonas aeruginosa is known to tolerate antibiotic therapy during infection. This prevents clearance of infection and negatively impacts patient outcomes. Here, we report the transcriptome sequence of antibiotic-treated and untreated P. aeruginosa cultures and the differential gene expression observed when treated cells are compared to untreated cells.
Project description:Using mouse models of acute and chronic Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection, combined with single-cell RNA sequencing (scRNA-seq), flow cytometry and fluorescent multiplex immunohistochemistry (mIHC) and other experimental strategies, we map immune changes and particular immune cell subtypes during acute and chronic infection.This integrated method profiled extensive cell atlas of healthy and infected mouse lungs and defined subpopulations of main immune cells not further subdivided before. We found that the proportions and status of several kinds of pulmonary immune cells were changed a lot after P. aeruginosa pulmonary infection.In particular, the percentage of neutrophils and CD200+ B cells increased significantly after acute infection, while interstitial macrophages (IMs) expanded distinctly during chronic infections, respectively. By analyzing public datasets, we have also found consistent findings of the changes of myeloid subpopulations in other bacterial and SARS-CoV-2 infections, thus arising a hypothesis that CD200+ B cells and IMs may play an unanticipated role in progression of infection diseases. Therefore, our findings provide novel perspectives for P. aeruginosa infection and have potential impact on the development of vaccines, antibiotics, and immunotherapeutic strategies when facing with pathogen challenges.
Project description:Airway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (MMP-7) and stromelysin-2 (MMP-10), two matrix metalloproteinases induced by acute P. aeruginosa pulmonary infection. Extraction of Differential Gene Expression (EDGE) analysis of gene expression changes in P. aeruginosa infected organotypic tracheal epithelial cell cultures from wildtype, Mmp7-/-, and Mmp10-/- mice identified 2,089 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to pseudomonas infection and show that a global genomics strategy can be used to assess MMP function. Experiment Overall Design: C57Bl6, Mmp7-/- and Mmp10-/- mouse epithelium at an organotypic air liquid interface culture was exposed to Pseudomonas aeruginosa for 1 and 24 h. RNA was collected from these samples as well as uninfected 0 h and assessed for expression changes using Affymetrix Mouse 430 2.0 Arrays. Triplicate samples were processed for each genotype at each time point.
Project description:Airway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (MMP-7) and stromelysin-2 (MMP-10), two matrix metalloproteinases induced by acute P. aeruginosa pulmonary infection. Extraction of Differential Gene Expression (EDGE) analysis of gene expression changes in P. aeruginosa infected organotypic tracheal epithelial cell cultures from wildtype, Mmp7-/-, and Mmp10-/- mice identified 2,089 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to pseudomonas infection and show that a global genomics strategy can be used to assess MMP function. Keywords: time course
Project description:To characterize the dynamic changes and differences of lung transcriptomic profiles induced by intratracheal infection of Neiserria subclava and Pseudomonas aeruginosa over a 14-day course.
Project description:Staphylococcus aureus and Pseudomonas aeruginosa are the most prevalent pathogens that colonize structurally abnormal airways such as those in Cystic Fibrosis (CF) and other chronic obstructive lung diseases. Although these bacteria seem to succeed one another, CF patients acquire coinciding P. aeruginosa and S. aureus pulmonary infections, being co-infection usually associated with decreased lung function and increased frequency of pulmonary exacerbations. In addition, P. aeruginosa and S. aureus pathogens adopt a biofilm mode of growth, which contributes to high tolerance to antibiotic treatment and the recalcitrant nature of these chronic coinfections, leading to significant patient morbidity and mortality. Interactions between P. aeruginosa and S. aureus have been widely studied and it is commonly admitted that P. aeruginosa outcompetes S. aureus, perhaps outcompeting S. aureus for limited nutrients or producing anti-staphylococcal compounds, having S. aureus a minimal contribution to the overall course of the infection. However, the molecular mechanisms behind these interactions are largely unknown. Herein, we decided to characterize the full transcriptome of these dual-species biofilms, to unveil important molecular interactions that can occur between these two bacterial species that are relevant for the pathogenesis of the entire consortia. Our data provide novel insights into the role of interspecies interactions in the pathogenesis of P. aeruginosa and S. aureus co-infections and will contribute to future studies by the research community.