Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing

Abstract Mycobacterium abscessus (Mab) is an emerging multidrug-resistant nontuberculous mycobacterium that causes a wide spectrum of infections and has caused several local outbreaks worldwide. To facilitate standardized prospective molecular surveillance, we established a novel core genome multilocus sequence typing (cgMLST) scheme. Over 2000 isolates of Mab, covering all subspecies and main dominant circulating clones as well as extra-pulmonary outbreak strains and sequential isolates of chronically infected cystic fibrosis patients, were used to validate the scheme and set genetic distance thresholds to delineate transmission events and global population structure. Most global clonal complexes previously classified using cgSNP were confirmed by our cgMLST approach, and also correlated well with traditional 7-loci MLST sequence types. 99% of pairwise comparisons between epidemiologically linked isolates were below 25 alleles and 90% below 10 alleles. These thresholds can be used for initial cluster analysis and to guide further epidemiological investigations. Overall, the scheme will help to unravel the apparent global spread of certain clonal complexes and as yet undiscovered transmission routes.