Non-tuberculous mycobacteria (MNT) cause chronic lung infections in individuals with cystic fibrosis (CF) and Mycobacterium abscessus (Mab) and Mycobacterium avium-intracellulare complex (MAC) are the most common species. MNTs form biofilms and when the thickness is > 40 nm, oxygen is no longer present, generating a condition of hypoxia. Hypoxia changes the metabolism of MNT cells from aerobic (A) to hypoxic (H), becoming less sensitive to drugs. To prevent these infections in CF, new antibiotic combinations must be found to kill A and H cells living in the hypoxic biofilm. The killing of Mab and MAC by combinations against A + H will be ascertained in aerobic, hypoxic and biofilm conditions, all found in persons with CF. Mab and MAC strains collected through the SMI-NTM network (Italian Multicentric Study – Non-tuberculous Mycobacteria) will be characterized by genome sequencing (WGA) and tested for drug activity. In this project, extension of previous FFC#12/2020, different drug combinations will be tested and the best ones will be tested against clinical isolates of Mab and MAC from CF in an attempt to sterilize A and H cells in the biofilm. Moreover, due to the little information on MNT dormancy, the expression of genes in Mab H cells will be studied. The goal of the project remains to find at least one combination that kills Mab and MAC A + H cells in vitro, to be explored in animal models to shorten long-term therapies of NMT infections in CF.

XIX Convention FFC Ricerca – download here a brief presentation of the project