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Genomic landscape of M. avium complex in Central Germany


N Wetzstein(1,2) M Diricks(2,3,4) T A Kohl(2,3,4) S Andres(3,4) M Kuhns(3,4) I Friesen(3,4) S Niemann(2,3,4) T A Wichelhaus(5)

1:Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; 2:Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; 3:German Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Germany; 4:National and WHO Supranational Reference Laboratory for Mycobacteria, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; 5:Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany

The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. Clinically, the most relevant ones are M. avium, M. intracellulare subsp. intracellulare (MINT) and M. intracellulare subsp. chimaera (MCH) causing pulmonary or disseminated infections. However, the population structure and genomic landscape of MAC remain little investigated. To address this, Illumina sequencing was performed on 328 MAC isolates from 185 German patients collected between 2006 and 2021 and set into context with publicly available MAC reference strains, as well as clinical data. Species were identified with NTMprofiler and sequences mapped to the according reference genomes M. avium ATCC 25291 or M. intracellulare ATCC 13950 with MTBseq. Overall, 229 isolates could be assigned to M. avium, 95 to M. intracellulare (46 MINT, 49 MCH), and two to M. marseillense. Although serial isolates showed high intrapersonal genetic stability, reinfection appeared to be a frequent event with 15/43 patients exhibiting genetically distinct MAC isolates (or even species) over the course of time. On the other hand, we identified clusters with less than 25 SNPs distance between genomes of isolates recovered from different patients, indicating possible transmission events both in M. avium and M. intracellulare. Interestingly, these clusters consisted of patients with a variety of underlying dispositions and clinical manifestations. In conclusion, this first comprehensive genomic study of MAC in a German cohort demonstrates that reinfection seems to be a frequent event, while clusters indicate possible person-to-person transmission or a common environmental source.

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