Mycobacterium abscessus genomic epidemiology in Northern Ireland, UK

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Background: Mycobacterium abscessus complex are non-tuberculous environmental mycobacteria that cause a spectrum of opportunistic human disease, especially in patients with underlying respiratory conditions and the immunosuppressed. Intrinsic resistance to many antibiotics makes treatment of M. abscessus infections very challenging and transmission within vulnerable groups, especially cystic fibrosis patients, is possible. Recent whole genome sequencing studies (Bronson et al, 2021; Diricks et al, 2022) have found M. abscessus is genomically diverse, although almost indistinguishable clonal strains have also been isolated from patients in different countries, suggesting international spread via as-yet unrecognised routes. No studies have been done to date in Northern Ireland to investigate genomic diversity of this pathogen, or possible transmission between patients. Methods: We performed whole genome sequencing on a collection of 48 M. abscessus strains isolated between 2021 and 2023 from 22 different patients in Northern Ireland. Speciation used a commercial (HAIN GenoType Mycobacterium CM v2.0) assay, compared to whole genome data. Conventional 7-locus multi-locus sequence typing (MLST), core genome multi-locus sequence typing (cgMLST) and core genome single nucleotide polymorphism (cgSNP) analyses were then used to compare isolates within and between patients. Results: 44/48 of isolates were identified as M. abscessus ssp. abscessus and 4/48 isolates (all from the same patient) were M. abscessus ssp. Massiliense, with 100% concordance between methods. 10 different MLST sequence types (ST5, ST9, ST23, ST24, ST34, ST39, ST40, ST97, ST101, ST108, and one new profile) and 14 different cgMLST sequence types were identified. There were three multi-patient clusters: ST5, ST9 and ST34. The ST5 (clonal complex 1) cluster was further resolved by cgMLST into 4 different sequence types, corresponding to 4 different patients within the cluster. However cgSNP analysis was required to resolve strains within both the ST9 (clonal complex 2) and ST34 clusters. Conclusions: This study confirms the usefulness of both conventional MLST and cgMLST to rule-out transmission between individual M. abscessus cases, but further cgSNP analysis was necessary to resolve strains within some sequence types.

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