Transglutaminase 2 (TG2) is a protein believed to play a crucial role in pathogenesis of cystic fibrosis (FC). It is a multifunctional enzyme involved in a variety of cellular processes, including the regulation of proteostasis, the process that ensures the correct balance and stability of proteins inside cells (biogenesis, maturation, trafficking and degradation). TG2 is activated in a dysregulated manner in the airways of CF patients and causes chronic inflammation, thus constituting a detrimental factor rather than beneficial in the pathogenesis of the disease. Several TG2 inhibitors can improve the picture of the disease like cysteamine, a molecule with the ability to control the hyperactivation of TG2 also improving the function of mutated CFTR. Cysteamine can improve the removal of Pseudomonas aeruginosa and pathogenic mycobacteria. The aim of this project is to clarify the molecular mechanisms with which cysteamine modulates susceptibility to infections in the airways in CF. Cysteamine activity against bacterial infection in mice infected with M. abscessus and P. aeruginosa and on CF patients blood cells will be evaluated. The results of the project will define the molecular basis that could support the use of cysteamine not only as a possible CFTR corrector but also as a therapy against bacterial infections in CF.