Metabolic network analysis of Pseudomonas aeruginosa during chronic cystic fibrosis lung infection.
System-level modeling is beginning to be used to decipher high throughput data in the context of disease. In this study, we present an integration of expression microarray data with a genome-scale metabolic reconstruction of Pseudomonas aeruginosa in the context of a chronic cystic fibrosis (CF) lung infection. A genome-scale reconstruction of P. aeruginosa metabolism was tailored to represent the metabolic states of two clonally related lineages of P. aeruginosa isolated from the lungs of a CF patient at different points over a 44-month time course, giving a mechanistic glimpse into how the bacterial metabolism adapts over time in the CF lung. Metabolic capacities were analyzed to determine how tradeoffs between growth and other important cellular processes shift during disease progression. Genes whose knockouts were either significantly growth reducing or lethal in silico were also identified for each time point and serve as hypotheses for future drug targeting efforts specific to the stages of disease progression.
Oberhardt
Matthew A
MA
Department of Biomedical Engineering, University of Virginia, Box 800759, Health System, Charlottesville, Virginia 22908, USA.
Goldberg
Joanna B
JB
Hogardt
Michael
M
Papin
Jason A
JA
D000222:Adaptation, Physiological; D001426:Bacterial Proteins; D018533:Biomass; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D008168:Lung / Q000382:microbiology; D010641:Phenotype; D040081:Protein Array Analysis; D011552:Pseudomonas Infections / Q000150:complications / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
D001426:Bacterial Proteins