The findings oh this study indicate that cysteamine can improve the clearance of pathogenic mycobacteria such as Mycobacterium abscessus and Pseudomonas aeruginosa. Moreover, it was found that TG2 is able to control the innate immune response by regulating type 1 interferon production, thus possibly explaining the negative role of the enzyme in the infection process. These results will define the molecular basis that supports the use of cysteamine not only as a CFTR corrector but also as a promising therapy against bacterial opportunistic infections. To understand the molecular pathway involved in bacterial infection could provide new possible targets and the possibility to define novel strategies aimed to improve the health care of CF patients.