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Contribution of Veillonella parvula to Pseudomonas aeruginosa mediated pathogenicity in a murine tumor model system

ABSTRACT: We investigated the specific interactions of the most dominant bacterial CF-pathogen, Pseudomonas aeruginosa, and the anaerobic bacterium Veilllonella parvula, that has been recovered at comparable cell numbers in the respiratory tract of CF patients. We used our recently established in-vivo murine tumor model to investigate mutual influences of the two pathogens during a biofilm-associated infection process. We found that although P. aeruginosa and V. parvula colonized distinct niches within the tumor, in mice that were co-infected with both bacterial species significant higher cell numbers of P. aeruginosa were recovered from the tumor tissue. Concordantly, in vivo transcriptional profiling implied that the presence of V. parvula supports P. aeruginosa growth at the infected host site, and the higher P. aeruginosa load correlated with clinical deterioration.

ORGANISM(S): Mus musculus Veillonella parvula DSM 2008 Pseudomonas aeruginosa PA14

PROVIDER: GSE58388 | GEO | 2014/11/06

SECONDARY ACCESSION(S): PRJNA252432

REPOSITORIES: GEO

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Contribution of Veillonella parvula to Pseudomonas aeruginosa mediated pathogenicity in a murine tumor model system

Project description:We investigated the specific interactions of the most dominant bacterial CF-pathogen, Pseudomonas aeruginosa, and the anaerobic bacterium Veilllonella parvula, that has been recovered at comparable cell numbers in the respiratory tract of CF patients. We used our recently established in-vivo murine tumor model to investigate mutual influences of the two pathogens during a biofilm-associated infection process. We found that although P. aeruginosa and V. parvula colonized distinct niches within the tumor, in mice that were co-infected with both bacterial species significant higher cell numbers of P. aeruginosa were recovered from the tumor tissue. Concordantly, in vivo transcriptional profiling implied that the presence of V. parvula supports P. aeruginosa growth at the infected host site, and the higher P. aeruginosa load correlated with clinical deterioration. We cultivated P. aeruginosa PA14 and V. parvula DSM No.:2008 in mono- and co-cultures in vivo using an established murine tumor model. Corresponding in vitro samples were generated under anaerobe growth conditions.

2014-11-06 | E-GEOD-58388 | biostudies-arrayexpress

miRNA expression in EBC

Project description:Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa.

2019-04-22 | GSE130159 | GEO

Ex vivo transcriptional profiling reveals a common set of genes important for the adaptation of Pseudomonas aeruginosa to chronically infected host sites

Project description:The opportunistic bacterium Pseudomonas aeruginosa is a major nosocomial pathogen causing both devastating acute and chronic persistent infections. During the course of an infection, P. aeruginosa rapidly adapts to the specific conditions within the host. In the present study, we aimed at the identification of genes that are highly expressed during biofilm infections such as in chronically infected lungs of patients with cystic fibrosis (CF), burn wounds and subcutaneous mouse tumours. We found a common subset of differentially regulated genes in all three in vivo habitats and evaluated whether their inactivation impacts on the bacterial capability to form biofilms in vitro and to establish biofilm-associated infections in a murine model. Additive effects on biofilm formation and host colonization were discovered by the combined inactivation of several highly expressed genes. However, even combined inactivation was not sufficient to abolish the establishment of an infection completely. These findings can be interpreted as evidence that either redundant traits encode functions that are essential for in vivo survival and chronic biofilm infections and/or bacterial adaptation is considerably achieved independently of transcription levels. Supplemental screens, will have to be applied in order to identify the minimal set of key genes essential for the establishment of chronic infectious diseases. Ex-vivo samples were collected from burn wound, cystic fibrosis patients mucous and mice tumor and stabilized for the RNA extraction. Recovered clinical strains were cultivated in rich medium control conditions untill the early stationary phase and RNA was extracted. The murine tumors were infected with burn wound isolated strains

2012-11-14 | E-GEOD-25945 | biostudies-arrayexpress

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

Novel virulence factors in host-adapted Pseudomonas aeruginosa infection of the Cystic Fibrosis airways

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

2010-11-04 | E-GEOD-25130 | biostudies-arrayexpress

Early defects of airway mucin sialylation and of mucociliary clearance at the onset of lung pathogenesis in a pig model of cystic fibrosis

Project description:Chronic infection of the lungs by bacteria such as Pseudomonas aeruginosa plays an important role in the natural history of Cystic Fibrosis (CF). Altered mucin secretions and glycosylations are hallmarks of bacterial infections but their exact contributions to the development of chronic infection and/or inflammation remain to be established. We studied the lung environment in newborn CFTR-/- pigs, which closely mirrors the human CF phenotype at the levels of mucin glycosylation, mucociliary transport (MCT) and immune response to P. aeruginosa infections. We show an increased sialylation of mucins from the tracheal mucosa of CFTR-/- pigs, which is also associated to increased Pseudomonas aeruginosa adherence. RNA-seq analysis did not show any altered expression of inflammatory genes, nor of sialylation enzymes. CFTR-/- piglets were unable to clear P. aeruginosa from the airways, leading to increased bacteria time of residence in the airways. We propose that alterations in mucin sialylation and MCT directly contribute to the early development of a favorable environment for bacterial colonization of the CF airways in the absence of an intrinsic inflammation.

2020-06-01 | GSE99862 | GEO

Novel virulence factors in host-adapted Pseudomonas aeruginosa infection of the Cystic Fibrosis airways

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. This SuperSeries is composed of the SubSeries listed below.

2010-11-04 | GSE25130 | GEO

Pseudomonas aeruginosa promotes persistence of Stenotrophomonas maltophilia via increased adherence to depolarized respiratory epithelium

Project description:In this study, we used host and bacterial RNA sequencing to evaluate the impact of dual species infections with S. maltophilia and P. aeruginosa on CF disease progression. To evaluate S. maltophilia transcript profiles we used a recently described method for selective capture of bacterial mRNA transcripts with strain specific RNA probes.

2022-11-04 | GSE216847 | GEO

Metabolic Phenotyping and Strain Characterisation of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients Using Rapid Evaporative Ionisation Mass Spectrometry

Project description:Rapid evaporative ionisation mass spectrometry (REIMS) is a novel technique for the real-time analysis of biological material. It works by conducting an electrical current through a sample, causing it to rapidly heat and evaporate, with the analyte containing vapour channelled to a mass spectrometer. It was used to characterise the metabolome of 45 Pseudomonas aeruginosa (P. aeruginosa) isolates from cystic fibrosis (CF) patients and compared to 80 non-CF P. aeruginosa. Phospholipids gave the highest signal intensity; 17 rhamnolipids and 18 quorum sensing molecules were detected, demonstrating that REIMS has potential for the study of virulence-related metabolites. P. aeruginosa isolates obtained from respiratory samples showed a higher diversity, which was attributed to the chronic nature of most respiratory infections. The analytical sensitivity of REIMS allowed the detection of a metabolome that could be used to classify individual P. aeruginosa isolates after repeated culturing with 81% accuracy, and an average 83% concordance with multilocus sequence typing. This study underpins the capacities of REIMS as a tool with clinical applications, such as metabolic phenotyping of the important CF pathogen P. aeruginosa, and highlights the potential of metabolic fingerprinting for fine scale characterisation at a sub-species level.

2022-01-26 | MTBLS644 | MetaboLights

P. aeruginosa PA14 gene expression in artificial sputum medium (ASMDM)

Project description:Pseudomonas aeruginosa airway infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. In vitro models that closely mimic CF sputum are needed to improve understanding of the pathobiology of P. aeruginosa in the CF airway. We developed an artificial sputum medium (ASMDM) that more closely resembles the composition of CF sputum than current media. In order to validate the utility of ASMDM, we used GeneChip microarrays to compare expression data of P. aeruginosa UCBPP-PA14 (PA14) in ASMDM with published data for this strain grown under the same conditions in an artificial medium containing 10% (v/v) CF sputum. Thirty-seven of 39 nutrition-related genes were differentially expressed in the same manner in both media. However, 24 quorum-sensing (QS) genes, 23 Type III secretion system and several anaerobic respiration genes were more highly expressed in ASMDM than in sputum-containing medium. When grown to stationary phase in ASMDM, PA14 differentially expressed about 50 biologically significant genes compared to stationary phase growth in Luria Broth; genes involved in iron acquisition (pfeA, fepC) and in assimilatory nitrate reduction (nasC, nirD) were upregulated, while 24 QS genes, including the regulator rhlR, lasA, rsaL, aprADEI and phenazine genes phzC2DD2EG2 were downregulated. Downregulation of QS-regulated virulence genes has been noted in chronic P. aeruginosa infection. ASMDM thus appears highly suitable for studies on gene expression of (i) P. aeruginosa strains from acutely and chronically infected CF patients and (ii) established biofilms that are a hallmark of advanced CF lung disease.

2010-05-31 | GSE18594 | GEO

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