Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen responsible for difficult-to-treat healthcare associated urinary tract infections, leading to relapses (chronic infections). While the adaptation mechanisms of P. aeruginosa in the respiratory tract are well studied, its adaptation and survival mechanisms in the urinary tract are very poorly understood. The aim of this PhD is to characterize P. aeruginosa survival and adaptation mechanisms to better understand the pathogenesis of recurrent urinary tract infections, using a collection of sequential urinary isolates collected from 3 patients for which genomic adaptations (mutations and large deletions) have been previously characterized over time. First, we will study the impact of the genomic modifications observed over time on the response of these isolates to various stresses encountered in the urinary environment (osmolarity, pH, oxidative stress), the capacity for long-term survival and intracellular survival in macrophages, and virulence in the Galleria mellonella larval infection model. Second, we will perform a comparative analysis of transcriptomes, proteomes and metabolomes of early and late Pseudomonas isolates in conventional growth medium and in urine (human pooled urine and artificial urine medium) to identify the regulatory pathways and metabolic mechanisms underlying the evolutionary adaptation of this species to urine. This would help to define new therapeutic strategies against this species frequently resistant to antibiotics.