Following the results obtained in the previous projects (FFC#12/2020 and FFC#17/2021), the research team aims to obtain new and more effective antibiotics active to combat infections by non-tuberculous mycobacteria (NTM). Among NTMs, Mycobacterium abscessus (Mab) is the most isolated species in chronic lung infections in individuals with cystic fibrosis (CF). It has been observed that Mabs, in the absence of oxygen (hypoxia), pass from the active replication (AR) to the non-replicative (NR) phase, in which they are tolerant to drugs. The aim of the project is therefore to identify new combinations of antibiotics to kill both AR and NR (anaerobes), which live in the hypoxic CF biofilm, containing drug-tolerant cells (persisters). Researchers will test various antibiotics, including those already available, such as colistin and ß-lactam antibiotics, and will also study the mechanisms responsible for the transition that leads to the creation of persisters at the gene level. The goal is to identify at least one combination capable of killing both AR and NR Mab cells in less than 1 month, which will then be explored in animal models and possible clinical studies, to shorten anti-Mab therapies in CF.