Project description:The gene expression of the opportunictic cystic fibrosis lung pathogen Burkholderia multivorans ATCC 17616 was investigated under different growth conditions relevant for growth in the cystic fibrosis lung.
Project description:The gene expression of the opportunictic cystic fibrosis lung pathogen Burkholderia multivorans ATCC 17616 was investigated under different growth conditions relevant for growth in the cystic fibrosis lung.
Project description:The gene expression of the opportunictic cystic fibrosis lung pathogen Burkholderia multivorans ATCC 17616 was investigated under different growth conditions relevant for growth in the cystic fibrosis lung.
Project description:The airways of cystic fibrosis patients are chronically colonized by a diverse range of microbial pathogens, the composition of which changes throughout life Alteration to the pulmonary environment caused by inter-microbial interactions and pathogen-host interactions influence the type of microbes that can engage in sustained infection. The opportunistic bacterial pathogen Pseudomonas aeruginosa is the primary cause of morbidity and mortality amongst individuals with cystic fibrosis and it is estimated that 60 – 80 % of cystic fibrosis patients experience chronic P. aeruginosa infection by the age of 20 years Aspergillus fumigatus is the most prevalent fungal pathogen isolated from cystic fibrosis airways, affecting up to 58% of patients. It is the causative agent of allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity disorder resulting from the inhalation of fungal conidia. Although co-colonization of the cystic fibrosis airways by P. aeruginosa and A. fumigatus is rare (3.1 – 15.8 %) disease prognosis is poor when both are present. However, sequential infection is more common. It has recently been suggested that A. fumigatus is more prevalent in juvenile cystic fibrosis patients that has been initially reported due to inconsistencies in the culture methods used to detect A. fumigatus. Despite the prevalence and persistence of A. fumigatus, P. aeruginosa predominates as the primary pathogen in the cystic fibrosis lung, suggesting that interactions with other pathogens such as A. fumigatus may influence the pathogenicity of P. aeruginosa by altering its virulence. We report here an investigation of the effect of culturing P. aeruginosa in the presence of A. fumigatus by measuring differences in growth rate and the overall proteome of the bacteria. It was hypothesized that A. fumigatus creates an environment that promotes a metabolic-driven increase in P. aeruginosa that results in it outcompeting the fungus. The molecular basis of this increased proliferation was investigated further using Label-free quantitative (LFQ) proteomics to characterise the proteome changes in P. aeruginosa when exposed to the supernatant of i) A. fumigatus alone ii) the supernatant of an A. fumigatus/P. aeruginosa co-culture and iii) P. aeruginosa alone. LFQ proteomics involves the simultaneous identification and quantification of thousands of proteins (the ultimate determinants of phenotype) from a single sample has recently been employed to characterise the P. aeruginosa proteome in response to iron limiting conditions, resolving how how the bacteria survives and proliferates in such environments.
Project description:Pseudomonas aeruginosa was repeatedly and intermittently exposed to tobramycin. Bacteria were grown in synthetic cystic fibrosis medium in wells of a 96-well microtiter plate. After 24 hours, more medium with or without tobramycin was added. After another 24 hours of incubation, a subsample of the well content was used to inoculate fresh synthetic cystic fibrosis medium in a 96-well microtiter plate. This was repeated for a total of 15 cycles. Evolved lineages were then DNA-sequenced to screen for genome changes.
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