Dataset Information

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection.

ABSTRACT: The airways of patients with cystic fibrosis (CF) are highly complex, subject to various environmental conditions as well as a distinct microbiota. Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and the predominant cause of morbidity and mortality in CF. A multifarious interplay between the host, pathogens, microbiota, and the environment shapes the course of the disease. There have been several excellent reviews detailing CF pathology, Pseudomonas and the role of environment in CF but only a few reviews connect these entities with regards to influence on the overall course of the disease. A holistic understanding of contributing factors is pertinent to inform new research and therapeutics.In this article, we discuss the deterministic alterations in lung physiology as a result of CF. We also revisit the impact of those changes on the microbiota, with special emphasis on P. aeruginosa and the influence of other non-genetic factors on CF. Substantial past and current research on various genetic and non-genetic aspects of cystic fibrosis has been reviewed to assess the effect of different factors on CF pulmonary infection. A thorough review of contributing factors in CF and the alterations in lung physiology indicate that CF lung infection is multi-factorial with no isolated cause that should be solely targeted to control disease progression. A combinatorial approach may be required to ensure better disease outcomes.CF lung infection is a complex disease and requires a broad multidisciplinary approach to improve CF disease outcomes. A holistic understanding of the underlying mechanisms and non-genetic contributing factors in CF is central to development of new and targeted therapeutic strategies.

SUBMITTER: Bhagirath AY

PROVIDER: S-EPMC5139081 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection.

Bhagirath Anjali Y AY Li Yanqi Y Somayajula Deepti D Dadashi Maryam M Badr Sara S Duan Kangmin K

BMC pulmonary medicine 20161205 1

<h4>Background</h4>The airways of patients with cystic fibrosis (CF) are highly complex, subject to various environmental conditions as well as a distinct microbiota. Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and the predominant cause of morbidity and mortality in CF. A multifarious interplay between the host, pathogens, microbiota, and the environment shapes the course of the disease. There have been several excellent reviews detailing CF pathology, P ...[more]

PMID: 27919253

Similar Datasets

Project description:BackgroundChronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review.ObjectivesTo assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013).Selection criteriaRandomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis.Data collection and analysisThe authors independently selected trials, assessed them and extracted data.Main resultsSix trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001).Authors' conclusionsVaccines against Pseudomonas aeruginosa cannot be recommended.

Project description:RationalePseudomonas aeruginosa, the predominant cause of chronic airway infections of patients with cystic fibrosis, exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity.ObjectivesTo characterize the population genetic structure of transmissible P. aeruginosa Liverpool Epidemic Strain in chronic infections of nine patients with cystic fibrosis, and infer evolutionary processes associated with adaptation to the cystic fibrosis lung.MethodsWe performed whole-genome sequencing of P. aeruginosa isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies.Measurements and main resultsGenome sequences were obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one patient sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional patients indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all patients indicated smaller genetic distances between than within patients in most cases.ConclusionsOur population-level analysis demonstrates that coexistence of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during chronic infection. The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for patient segregation and therapeutic strategies.

Dataset Information

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection.

Publications

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets