Deciphering the role of Polyamines, key metabolites in virulence of P. aeruginosa and its interaction with S. aureus – POPS

The POPS project aims to elucidate the role of polyamines in bacterial virulence, focusing on the pathogens Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa). These bacteria are responsible for acute and chronic respiratory infections, especially in patients with cystic fibrosis (CF) and are frequently found together. Polyamines are essential metabolites present in both prokaryotes and eukaryotes. Elevated levels of polyamines have been associated with increased virulence of Pa and respiratory function instability in CF patients (Moyne et al. 2021). Furthermore, our preliminary data show that the presence of Sa alters the metabolism of polyamines in both species. For the first time, the project explores an alternative pathway for polyamine production in Pa, regulated by the two-component system, PmrAB. The research program is organized into four workpackages (WP1-4) and a management workpackage (WP0). WP1 focuses on the role of polyamines in Pa virulence, using genetic engineering, targeted metabolomics, and phenotypic characterization tests of Pa virulence in vitro and in vivo. WP2 examines the impact of polyamines on the physiology of Sa. WP3 employs advanced metabolomics techniques to characterize metabolic changes in Sa exposed to polyamines. In WP4, the use of comparative genomics will allow us to understand the evolutionary origins and distribution of polyamine biosynthesis pathways in bacteria. Through a multidisciplinary consortium (Pa and Sa virulence, metabolomics and other omics, genetics, and computational biology), the project aims not only to elucidate the action of polyamines, but also their role in microbial competition within the respiratory community, paving the way for the development of new generations of therapeutic interventions.