Cystic fibrosis (CF) is a genetic disorder caused due to mutations in the CF transmembrane conductance regulator (cftr) gene. Mutations in the cftr gene result in altered ion transport, viscous mucus and inflammation in the airways. Viscous mucus is very rich in nutrients thus becoming a favourable environment for microbes. Microbial colonization of CF lungs requires various mechanisms of adaptation and is crucial for establishment of chronic lung infections by pathogens. Pseudomonas aeruginosa is an opportunistic pathogen and one of the main colonisers of the CF lung. We have previously isolated and genome sequenced several P. aeruginosa isolates (PASS1-4) from Australian CF patient’s sputum. Genomic analysis indicated that, as expected, these strains shared a large set of core genes with the laboratory strain PAO1. Phenotype assays for carbon utilization using Biolog Phenotype Microarrays indicated that P. aeruginosa strain PASS4, compared to other CF strains and PAO1, utilizes a very narrow range of sole carbon sources. Increased cellular respiration of strain PASS4 was only observed in the presence of inosine and adenosine, which are components of the DNA backbone. CF lung environment is rich in mucins, salts, amino acids and DNA. The latter originates from both dying host cells and bacteria. The preference for using mainly DNA related carbon sources may imply that strain PASS4 can be highly adapted to the CF lung. In order to elucidate the molecular pathway/s unique to strain PASS4 and the gene expression essential for its adaptation transcriptomic and proteomic analysis has been conducted of PASS4 grown in DNA and an amino acid as a control. Growth on DNA resulted in the up-regulation of an array of genes involved in virulence and biofilm formation which may indicate that sensing external DNA is a trigger in the expression of virulence traits.