Pseudomonas aeruginosa (PA) is an important bacterial pathogen causing a wide range of acute and chronic infections (CI). It usually expresses a yellow-green pigment. It is a major cause of respiratory CI in patients with underlying diseases such as cystic fibrosis (CF) leading to a progressive lung damage. Pathogenesis in CI implies a genetic diversification of PA, with emergence of atypical mutants such as brown pigment producing PA (bpPA). PACI study aims to explore the adaptation process of PA in CI, through the example of bpPA and to evaluate the clinical outcome of the emergence of such mutants. Ten clinical (CF and non-CF) or laboratory bpPA, and their isogenic yellow-green counterparts, have been identified. Preliminary data showed a large deletion in the same chromosomal region in bpPA when compared to their parental strains. Deleted genes are involved in chimiotactism, metabolism, resistance to antibiotics, synthesis of lipopolysaccharides, biofilm formation, anaerobic respiration and regulation. This strongly suggests that bpPA deeply modify their behaviour and virulence strategy in patients. The applicant will identify the deleted genes in bpPA using comparative genomic DNA hybridization microarrays and to assess variations in resistance to antibiotics and pyocins, growth under diverse conditions, metabolism, motility and virulence factor production. He will correlate the emergence of bpPA in CF-patients with disease progression using existing clinical data and bacterial collection. This proposal will permit the fellow, now in position of Associate Professor/Hospital Practitioner in the Dpt of Bacteriology, University of Franche-Comté (Besançon, France), to conduct the project during 2 years in the Dpt of Microbiology, University of Washington (Seattle, USA) before resuming his position in France. Characterization of these chronically-adapted clinical isolates will contribute to define new therapeutical options for the treatments of CI due to PA.
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