Target Validation (WP4, WP5, WP6)
Uses a multifaceted approach, by a sequential cascade of models including human cell lines wild type or carrying CFTR mutations, the nematode worm Caenorhabditis elegans and mouse models both for acute and chronic infection, either to provide the rationale and the proof-of-concept for the characterization and validation of selected targets as candidates for the development of antibacterials.This project will also reveal the role in virulence of a significant number genes of unknown function in the genome of P. aeruginosa as well as invaluable insights into their conservation across different clinical isolates of this organism. Target validation is carried out in a collection of P. aeruginosa clinical strains of different origins and searched in other gram negative bacteria such as B. cenocepacia strains by multiple genome sequence and comparative analysis. This is expected to provide a panel of targets with a global relevance and considered a critical step in terms to provide solid rationale to further proceed with the project towards the target inhibition.