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Pseudomonas aeruginosa

ABSTRACT: Chronically Infected Cystic Fibrosis Lungs Genome Sequencing

PROVIDER: PRJNA252385 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1374940_1.fastq.gz	Fastqsanger.gz
	SRR1374940_2.fastq.gz	Fastqsanger.gz
	SRR1374950_1.fastq.gz	Fastqsanger.gz
	SRR1374950_2.fastq.gz	Fastqsanger.gz
	SRR1374960_1.fastq.gz	Fastqsanger.gz

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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

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Project description:Pseudomonas aeruginosa is an environmentally resilient bacterium and an important cause of both acute and chronic infections in people with impaired natural barriers or immunological defences. Chronic respiratory infection with P. aeruginosa is a major cause of morbidity and mortality in people with airway diseases, including cystic fibrosis and bronchiectasis. Chronic airway infection is characterised by periods of relative stability punctuated by pulmonary exacerbations, during which times rapid bacterial outgrowth necessitates intense antimicrobial chemotherapy. The periods of stable infection can be modelled in mice, by nasal instillation of airway-adapted P. aeruginosa in saline, leading to prolonged colonisation of both upper airway (sinus) and lower airway (lung) environments that is not associated with symptomatic disease. Here, we use NMR metabolomics to investigate the impact of P. aeruginosa colonisation on the metabolic landscape of sinuses and lungs. Lung infection led to pronounced changes in the airway metabolome, with depletion of glucose and myo-inositol but enrichment of glutathione, relative to uninfected lungs. Changes in the sinuses were more subtle but could be identified through dimensionality reduction approaches. The NMR spectral peaks which discriminated between infected and uninfected sinuses in partial least squares discriminant analysis included those for lactate and choline but were mostly representative of yet unidentified metabolites. These data highlight the differential impact of infection on separate airway compartments and identify undefined metabolites undergoing pronounced abundance changes during infection.

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