Metabolism of Pseudomonas aeruginosa under conditions of persistent infection of the cystic fibrosis lung

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Pseudomonas aeruginosa causes persistent lung infections of patients suffering from the genetic disorder cystic fibrosis (CF). It is the dominant bacterium in the sputum of chronically infected CF lungs and often associated with poor prognosis of the patients. Much is known about P. aeruginosa virulence factors and its ability to grow as biofilms during infection. However, the metabolic basis for success of P. aeruginosa in colonization, adaptation and establishing a persistent infection is only partly understood. One reason for this lack of knowledge is that CF-sputum as well as growth conditions in the CF-sputum are difficult to mimic. Consequently, the physiology and the corresponding metabolism of P. aeruginosa under persistent infection conditions are currently unknown, however, of high relevance for the success of this pathogen. Recently, we started the investigation of the P. aeruginosa transcriptome, proteome and metabolome using an artificial sputum medium. We determined metabolic profiles of P. aeruginosa, determined the metabolic pathways in operation during anaerobic growth. In this application we aim to complement our current data with equivalent information for P. aeruginosa grown on CF patient sputum. We will identify the carbon sources crucial for successful growth in CF sputum under microaerobic and anaerobic conditions. We will test how different carbon sources change the physiology, virulence and antibiotic tolerance of P. aeruginosa. A model of the metabolic and regulatory network will be deduced, tested and further developed into a systems biology approach. Furthermore, we will compare the metabolism of P. aeruginosa laboratory strains to clinical isolates adapted to the CF-lung habitat. Results of these studies will shed light on the metabolic strategies employed by P. aeruginosa for the adaptation to conditions in the CF lung. We hope to understand if typical CF mutant phenotypes are caused by this metabolic adaptation process. Clearly, this combined experimental and partly modeled approach will provide a novel rationale to develop alternative strategies and discover new targets for antibiotics to treat P. aeruginosa infections.