Objective 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. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics Keywords Adaptation Chronic infections Cystic fibrosis Genomic Microbiology Pseudomonas aeruginosa Virulence Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-IOF-2008 - Marie Curie Action: "International Outgoing Fellowships for Career Development" Call for proposal FP7-PEOPLE-IOF-2008 See other projects for this call Funding Scheme MC-IOF - International Outgoing Fellowships (IOF) Coordinator UNIVERSITE DE FRANCHE-COMTE EU contribution € 334 410,20 Address 1 RUE CLAUDE GOUDIMEL 25000 Besancon France See on map Region Bourgogne-Franche-Comté Franche-Comté Doubs Activity type Higher or Secondary Education Establishments Administrative Contact Fournier Pauline (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
