Insights on the Pathogenesis of Mycobacterium abscessus Infection in Patients with Cystic Fibrosis

People with CF (pwCF) have a significant risk for pulmonary infections with non-tuberculous mycobacteria (NTM), particularly Mycobacterium abscessus (Mab). Mab is an emerging pathogen, which causes pulmonary infections in patients with chronic lung diseases, particularly CF; Mab pulmonary disease leads to progressive pulmonary dysfunction and increased morbidity and mortality. Despite advances in CF care, including CFTR modulators (CFTRm), Mab continues to pose a therapeutic challenge, with significant long-term medical burden. This review provides insights into the complex host–pathogen interplay of Mab infections in pwCF. It provides a detailed overview of Mab bacterial virulence factors, including biofilm formation, secretion systems, the virulence-associated rough morphotype, and antibiotic resistance mechanisms. This review also summarizes features conferring susceptibility of the CF host to Mab infections, alongside the contribution of the CF-host environment to the pathogenesis of Mab infection, such as antibiotic-derived microbial selection, within-host mycobacterial evolution, and interactions with co-pathogens such as Pseudomonas aeruginosa (PA). Finally, the therapeutic implications and novel treatments for Mab are discussed, considering the complex host–pathogen interplay.