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However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009386), MCH (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009111), and MINT (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200977). 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\u20130.28,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 and OR 0.11 95% CI 0.02\u20130.4,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004, respectively)\u00a0and 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%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-024-01359-8","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T05:02:12Z","timestamp":1720501332000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Clinical and genomic features of Mycobacterium avium complex: a multi-national European study"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-4668","authenticated-orcid":false,"given":"Nils","family":"Wetzstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margo","family":"Diricks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Anton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6nke","family":"Andres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kuhns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Kohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kehrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara C.","family":"Kahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz K.","family":"Jansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie A.","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Schulthess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hogardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Friesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Niemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Wichelhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"issue":"11","key":"1359_CR1","doi-asserted-by":"publisher","first-page":"3666","DOI":"10.1099\/ijsem.0.003026","volume":"68","author":"J van Ingen","year":"2018","unstructured":"van Ingen J, Turenne CY, Tortoli E, Wallace RJ Jr, Brown-Elliott BA. 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Jan Kehrmann received honoraria for lectures and support for travel from INSMED outside the submitted work. Michael Hogardt reports grants from Mukoviszidose Institut gGmbH and the German Federal Ministry of Health, honoraria for lectures from the Landes\u00e4rztekammer Hessen and bioM\u00e9rieux, and funding from Merck AG outside the submitted work. Thomas A. Wichelhaus reports research grants from BMBF, JPIAMR, Deutsche Krebshilfe, MSD as well as speaker fees and consulting honoraria from Insmed, Osartis, all outside the submitted work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}