IRONEX

The IRONEX project aims to investigate the role of Resistance-Nodulation-cell-Division (RND) efflux systems in the secretion of siderophores, which are iron-chelating compounds, and their impact on antibiotic resistance and virulence in fluorescent-Pseudomonas species, includingPseudomonas aeruginosa. This latter is an opportunistic pathogen which is major of concern in human due to its high levels of resistance to antibiotics. The project aims to identify the specific RND efflux pumps responsible for the secretion of key siderophores, such as pyoverdine and secondary siderophores. Additionally, the project will investigate the function of these RND efflux pumps in closely related rhizospheric fluorescent Pseudomonas species, which play a significant role in plant health by promoting iron uptake. To achieve these objectives, we will construct genetic deletion mutants of key efflux pump genes in P. aeruginosa and complementary strains to determine their role in siderophore secretion. Similar approaches will be used to analyze efflux pump systems in rhizospheric Pseudomonas strains, with a focus on understanding their ecological and functional significance. Metabolomic and phenotypic studies will characterize the specific metallophores exported by these efflux pumps and their potential influence on resistance to cefiderocol, a novel siderophore-antibiotic. Laboratory experiments using clinical samples, including urine and expectorations, will assess the relationship between efflux pump activity, resistance, and virulence. In parallel, the beneficial roles of efflux pumps in promoting plant growth and iron uptake will be tested using rhizospheric strains and plant models under controlled conditions. This project is highly relevant to HARMI’s mission, as it connects clinical and environmental microbiology to enhance our understanding of microbial adaptation and interactions. By exploring the dual role of RND efflux pumps in antibiotic resistance and plant-microbe interactions, the project aims to guide the development of innovative therapeutic strategies to combat multidrug-resistant infections, particularly those caused by P. aeruginosa. By elucidating the molecular mechanisms of siderophore secretion and efflux pump function, IRONEX will contribute to the development of targeted antimicrobial strategies and new insights into the ecological roles of microbial communities.