Phenotype-Modeling Exploiting iron uptake pathways in P. aeruginosa to deliver drugs: phenotypic switches and mathematical modeling

One of the bottlenecks in antibiotic development is the ability of the drugs to enter bacteria. Iron uptake pathways can be used as gates to transport antibiotics into bacteria. To get access to iron, an essential nutrient, bacteria synthesize siderophores, small organic iron chelators. Antibiotics can be attached to siderophores. Consequently, when the pathogen takes up ferric siderophore, it also imports the antibiotic. The development of such compounds still suffers from a low knowledge on how bacteria adapt themselves in the presence of siderophore-antibiotic conjugates. In the present project, (i) phenotypical adaptation of bacteria to the presence of siderophore-antibiotic conjugates and different siderophores will be investigated on Pseudomonas aeruginosa used as a model, and (ii) knowledge acquired by the experiments will be used to develop a mathematical model to decipher the regulatory network and help to identify the most promising iron uptake pathway(s) for antibiotic vectorization.