Project description:To determine if differences in the severity of pulmonary infection in cystic fibrosis been seen in late isolates od Pseudomonas aeruginosa and Burkholderia cepacia are associated with differences in the initial repsonse of alveolar macrophages (AM) to these pathogens, we assessed gene expression changes in human AM in response to infection with a laboratoty strain, early and late clinical isolates of P. aeruginosa, and B. cepacia. Keywords: Comparison of gene expression in alveolar macrophages of normal non-smokers and normal smokers.
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:To determine if differences in the severity of pulmonary infection in cystic fibrosis been seen in late isolates od Pseudomonas aeruginosa and Burkholderia cepacia are associated with differences in the initial repsonse of alveolar macrophages (AM) to these pathogens, we assessed gene expression changes in human AM in response to infection with a laboratoty strain, early and late clinical isolates of P. aeruginosa, and B. cepacia. Experiment Overall Design: Alveolar macrophages were obtained from bronchoalveolar lavage. Experiment Overall Design: Two clinical strains isolated from the sputum of an individual with CF, AD2A and AD15B (provided by J. Burns, University of Washington, Seattle). AD2A is an early clinical isolate, and AD15B is a late clinical isolate; both were derived from the same individual.
Project description:Pseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Existing experimental data in our lab showed significantly different levels of virulence of "early" and "late" P. aeruginosa infection isolates in a C. elegans slow killing model. We wished to examine the expression profile of these isolates in order to explore genes that may be responsible for the observed differences. The expression profiles of two pairs of isolates (four isolates in total) were compared to each other using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating virulence in these isolates. Data analysis was carried out using BIOCONDUCTOR software. Keywords: Comparative strain hybridization
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 chronically colonizes the lungs of individuals with CF, where it reaches high cell densities and produces a battery of virulence factors. Upon infection, a single strain of P. aeruginosa can colonize an individual’s lungs throughout his or her lifetime. To understand the evolution of P. aeruginosa during chronic lung infection, we conducted both genotypic and phenotypic analyses on clinical isogenic strains obtained from the lungs of three different individuals with CF. These strains were isolated over a period of approximately ten years and possess phenotypes that are commonly observed in isolates from the CF lung, such as the antibiotic resistant dwarf and mucoid phenotypes. Microarray analyses were carried out on isolates grown in a chemically defined medium that mimics the nutritional environment of the CF lung, synthetic CF sputum medium (SCFM).
Project description:Pseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Existing experimental data in our lab showed significantly different levels of virulence of "early" and "late" P. aeruginosa infection isolates in a C. elegans slow killing model. We wished to examine the expression profile of these isolates in order to explore genes that may be responsible for the observed differences. The expression profiles of two pairs of isolates (four isolates in total) were compared to each other using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating virulence in these isolates. Data analysis was carried out using BIOCONDUCTOR software. Keywords: Comparative strain hybridization Two pairs of isolates (four isolates in total) were compared to each other when grown on Nematode Growth Medium (NGM).
Project description:Pseudomonas aeruginosa is a common pathogen in the lungs of the cystic fibrosis patients. As infection develops the organism progressively adapts to its environment and its mode of pathogenesis alters, frequently including the loss of quorum sensing (QS) regulated virulence factors. We used microarrays to determine genomic differences by comparative genome hybridisation between two P. aeruginosa isolates from CF patients, one of which exhibited an active quorum sensing (QS) system (UUPA38) typical of early acute infection while the other was QS-compromised (UUPA85) typical of chronic CF-adapted infection.
Project description:Pseudomonas aeruginosa chronically colonizes the lungs of individuals with CF, where it reaches high cell densities and produces a battery of virulence factors. Upon infection, a single strain of P. aeruginosa can colonize an individualâs lungs throughout his or her lifetime. To understand the evolution of P. aeruginosa during chronic lung infection, we conducted both genotypic and phenotypic analyses on clinical isogenic strains obtained from the lungs of three different individuals with CF. These strains were isolated over a period of approximately ten years and possess phenotypes that are commonly observed in isolates from the CF lung, such as the antibiotic resistant dwarf and mucoid phenotypes. Microarray analyses were carried out on isolates grown in a chemically defined medium that mimics the nutritional environment of the CF lung, synthetic CF sputum medium (SCFM). 17 clinically isolated P. aeruginosa strains from three individuals with CF (5 strains from individual P1, 7 strains from individual P2, 5 strains from individual P3). Two reference strains PAO1 and PA14. All experiments were biologically duplicated.