Journal Article

Clinical and genomic features of Mycobacterium avium complex: a multi-national European study

Lewin, Astrid, Kehrmann, Jan, Kahl, Barbara C., Schulthess, Bettina, Kuhns, Martin, Kohl, Thomas A., Wetzstein, Nils, Baron, Sophie A., Anton, Thomas B., Hogardt, Michael, Diricks, Margo, Andres, Sönke, Friesen, Inna, Zimmermann, Stefan, Jansson, Moritz K., Niemann, Stefan, Schmidt, Annika, Wichelhaus, Thomas A., Schwarz, Carsten

2024

Overview

Background The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated. Methods Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort. Results Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV ( n  = 386), MCH ( n  = 111), and MINT ( n  = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04–0.28, p  < 0.001 and OR 0.11 95% CI 0.02–0.4, p  = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%). Conclusions This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Antibiotics / Bacterial genetics / Bacteriology / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cardiology and cardiovascular system / Cluster analysis / DNA sequencing / Drug Resistance, Bacterial - genetics / E coli / Emerging diseases / Europe / Female / Genes / Genetic aspects / Genome, Bacterial / Genomes / Genomics / Genomics - methods / Health aspects / Heart surgery / Human Genetics / Human health and pathology / Humans / Infectious diseases / Life Sciences / Lung diseases / MAC / Male / Medicine/Public Health / Metabolomics / Methods / Microbiology and Parasitology / Middle Aged / Mycobacterium avium / Mycobacterium avium complex / Mycobacterium avium Complex - genetics / Mycobacterium avium Complex - isolation & purification / Mycobacterium avium-intracellulare Infection - epidemiology / Mycobacterium avium-intracellulare Infection - microbiology / Mycobacterium chimaera / Mycobacterium intracellulare / Non-tuberculous mycobacteria / Nosocomial infections / Nucleotide sequencing / Parasitology / Patients / Phylogenetics / Phylogeny / Plasmids / Plasmids - genetics / Polymorphism, Single Nucleotide / Population structure / Rifamycins / Single-nucleotide polymorphism / Systems Biology / Tuberculosis / Virology / Virulence / Virulence (Microbiology) / Virulence - genetics / Whole Genome Sequencing