Mycobacterium avium complex (MAC) genomics and transmission in a London hospital

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis (BX). Whilst recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. We sequenced 1000 Mycobacterium avium complex (MAC) isolates from CF and non-CF patients at the Royal Brompton Hospital (RBH), London. Epidemiological links were identified from patient records. Previously published genomes were used to characterise global population structures. Analysis of the three most predominant MAC species identified putative transmission clusters that contained patients with CF, BX and other lung conditions, although few epidemiological links could be identified. For M. avium, lineages were largely limited to single countries, whilst for M. chimaera, global transmission clusters previously associated with heater cooler units (HCUs) were found. However, the origin of the major HCU-associated outbreak was a lineage already circulating in patients with pre-existing lung conditions. CF and non-CF patients share transmission chains even in the presence of CF patient-focussed hospital control measures, although the lack of epidemiological links suggests that most transmission is indirect and may be due to environmental foci or else asymptomatic carriage in the wider population. The major HCU-associated M. chimaera lineage being derived from an already circulating lineage, suggests that HCUs are not the sole vector nor the ultimate source of this lineage. Future studies should include sampling of environmental reservoirs and potential asymptomatic carriers.