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COLQUE, Antonella

Director: Andrea Smania

PhD Thesis Topic

Analysis of adaptive mutations involved in the evolution of Pseudomonas aeruginosa in chronic airway infections and their relationship to hypermutability

Our project is based on the study of the bacterium Pseudomonas aeruginosa and its role as an opportunistic pathogen in chronic airway infections in cystic fibrosis (CF) patients. In this context, P. aeruginosa triggers a genetic adaptation process that underlies phenotypic diversification, which favor its long term persistence. Although antibiotics are key components of our antimicrobial armament for the treatment of infectious diseases, the current global threat of resistance in P. aeruginosa mainly results from its extraordinary ability to develop resistance to almost any available antibiotic by the selection of mutations in chromosomal genes. A trait frequently observed in chronic infections is an increased mutation rate leading to a mutator phenotype. P. aeruginosa from chronically infected CF airways was the first natural model to reveal a high proportion of mutators due essentially to inactivation of the mismatch repair system (MRS) through lost-of-function mutations in the antimutator mutS and mutL genes. Our goal is to investigate mutations in genes that confer resistance to antibiotics that occurred spontaneously in different clones but derivatives of the same P. aeruginosa mutator lineage isolated from the same CF patient after a long-term evolutionary process. It thus aims to determine the relationship among these mutations, hypermutability and the adaptability of the bacteria by analyzing their implication in the antimicrobial resistance.