The bleakest outlook for a "post-antibiotic era" is one in which microbial infections can no longer be cured. The traditional antibiotic pipeline has been exhausted, while antimicrobial resistance has become a multifaceted crisis, imposing a serious threat to global health. There is thus an urgent need for new antimicrobial treatments. Inspired by nature, antimicrobial peptides (AMPs) are gaining attention for their clinical translation, as they present distint advantages compared to conventional antibiotics. AMPs have shown a pivotal role in the innate immune system of living organisms; many of them are evolutionarily conserved with limited propensity to induce resistance. The main goal of this project is to fully characterize and optimize existing AMPs, i.e. esculentin peptides, against the Gram-negative bacterium Pseudomonas aeruginosa, which represents a serious life threat especially in cystic fibrosis sufferers. In fact, in the lung of these patients it grows in a sessile community (biofilm) that traditional antibiotics are not able to eradicate. We propose to pursue an experimental plan aimed at studying the antibiofilm potency of the selected AMPs on a panel of P. aeruginosa strains under conditions that better reflect physiology of the target districts as well as to assess their stability in biological fluids before testing their safety in mice. Furthermore, the project aims at exploring the effect of these AMPs on the host cells that are present at the sites of infection in terms of metabolic and immunomodulatory activities which represent hitherto unexplored aspects. Another relevant objective of the project is the characterization of novel nanoparticulate systems to prolong AMPs lifespan.
If successful, our multidisciplinary approach will allow a deeper understanding of the effectiveness of Esc peptides-based therapeutic formulation for the translation into real-life medicine to fight the current alarming antibiotic-resistant infectious diseases.
