Although considered sterile until a few years ago, the lungs of healthy individuals are now known to host a broad collection of microorganisms (termed lung microbiome). Alterations of this microbial community have been correlated with various respiratory infections, including in patients with chronic airway diseases (e.g. cystic fibrosis and chronic obstructive pulmonary disease). Nevertheless, the role of these microorganisms in the infectious disease process of respiratory pathogens as well as their therapeutic potential has been poorly investigated. In this project, I propose to investigate the anti-virulence potential of individual microbiome members in order to exploit them as novel therapeutic strategies to treat chronic lung infections with Pseudomonas aeruginosa. A combination of high-throughput screening and clinical study using patient samples will be exploited to identify bacteria with anti-virulence properties. State-of-the-art in vitro and in vivo models that are highly relevant for the chronic infection process of P. aeruginosa will be used to validate candidate microbiome members. The mode of action of the most promising candidate will be investigated through a targeted approach aimed at identifying the bioactive molecule(s) responsible for the observed anti-virulence effect. Based on the promising preliminary data from the host lab, it is anticipated that this project could lead to much-needed therapeutic solutions against P. aeruginosa.