From colonisation to chronicity: adaptation of Mycobacterium abscessus in the cystic fibrosis lung environment

Chronic infection by opportunistic pathogens is a major contributor to mortality inpeople with cystic fibrosis (CF). These infections are caused by antimicrobial resistant(AMR) pathogens such as the emerging pathogen, Mycobacterium abscessus, anontuberculous mycobacteria (NTM) which causes recalcitrant infections with highresistance to antibiotics. M. abscessus adapts over time of colonisation to theconditions in the CF lung, hampering effective treatment. The mechanisms underlyingthis pathoadaptation are poorly understood and are critical for the development offuture therapies. Sequential isolate pairs of M. abscessus from three people with CFwere examined for adaptive changes over time of infection. Genomic analysisconfirmed that these isolate pairs were clonal. The late infection isolates showedincreased host cell attachment to CF bronchial epithelial cells and increasedintracellular survival in macrophages, indicative of adaptation to the CF lungenvironment. Late isolates also showed changes in their proteomes, includingincreased abundance of proteins with roles in intracellular survival and antibioticresistance. Overall, it is clear that M. abscessus can adapt to the CF lung environmentand improve its ability to interact with host cells.