Optimized in vivo and ex-vivo Models as Platforms for the Preclinical Evaluation of Antimicrobial lead Compounds

The Project aims to develop and optimize in vivo and similar-vivo models useful as platforms to evaluate the therapeutic and toxic potential of antimicrobial drug candidates (e.g., pro-, pre-, and post-biotics, peptides) coming from the experimental activity of the other groups belonging to the Consortium. Specifically:  The invertebrate G. mellonella will be tested for effectiveness in antibacterial and toxicity evaluations of drug candidates; it could represent a valuable platform for high-throughput screening (HTS) of compounds with anti-P. aeruginosa potential.  A murine model of acute and chronic P. aeruginosa lung infection will be optimized to allow the evaluation of the efficacy of compounds effective at G. mellonella-based HTS.  An advanced cell culture model—i.e., lung-on-a-chip—will be improved to assess anti-P. aeruginosa compounds under conditions relevant to cystic fibrosis lungs. The work plan of the Project has been organized into 6 work packages (WPs) to achieve these specific objectives: WPs 1-2-3-4 containing a coherent set of activities (Tasks) aimed at optimizing in vivo and ex vivo preclinical platforms, WP5 aimed at validating antibacterial and safety of some products coming from the Consortium, and a central work package (WP6) on the management and coordination of the activities. This Project fits specific objective #5, “Messa a punto di modelli complessi similar-vivo e modelli animali di infezione.” It is aimed at reducing the gap between the results of scientific research and those of application for clinical and industrial purposes. The Project, therefore, meets the main aim set by Spoke 7 “Innovating Translational Medicine” consisting of collecting and linking proof-of-concept projects focused on different steps of a translational approach to infectious diseases, including those caused by multidrug-resistant bacteria, such as P. aeruginosa.