Cystic Fibrosis (CF) lung infections’ unresponsiveness to antibiotics and symptom recrudescence are largely due to the development of bacterial persistent forms. These specialized cells, including the so-called Viable But Non-Culturable (VBNC) cells, are dormant forms able to tolerate antibiotic treatment, hindering infection clearance. This is particularly true for Pseudomonas aeruginosa, the main pathogen for CF patients, whose persistent forms have been shown to be induced by different antibiotic classes. The novel siderophore cephalosporin cefiderocol, exploiting the bacterial iron-uptake systems to enter the cells, presents a greater efficacy compared to other known β-lactams and constitutes a highly desirable therapeutic option in CF.

However, little is known about the cefiderocol activity against P. aeruginosa persisters. This project aims to fill this knowledge gap, investigating in detail the P. aeruginosa response to treatment with cefiderocol. To achieve this goal, both in vitro biofilms and in vivo animal models of infections will be used, allowing a full understanding of P. aeruginosa population dynamics when exposed to cefiderocol. 

The results obtained in this project will provide an evaluation of P. aeruginosa persistence to cefiderocol, evidencing the drug contribution to the induction of specialized phenotypes, like culturable persisters and VBNC cells. These data will shed light on the drug efficacy to counteract P. aeruginosa infection and, consequently, on the population dynamics occurring in the CF lung environment, related to the risk of infection due to the persisters induction.