Molecular epidemiology of multi- and extensively-drug-resistant Mycobacterium tuberculosis in Ireland, 2001–2014

•Prevalence of MDR/XDR-TB in Ireland, while low, still poses a threat to Public Health.•High lineage diversity was found among MDR/XDR-TB strains.•“Cross-border” European Union strains have been found in Ireland.•Evidence of in vivo micro-evolution of strains was found during the study.•Putative transmission between an Irish-born patient and a non-Irish born patient was discovered. The primary objective of this work was to examine the acquisition and spread of multi-drug resistant (MDR) tuberculosis (TB) in Ireland. All available Mycobacterium tuberculosis complex (MTBC) isolates (n = 42), from MDR-TB cases diagnosed in Ireland between 2001 and 2014, were analysed using phenotypic drug-susceptibility testing, Mycobacterial-Interspersed-Repetitive-Units Variable-Number Tandem-Repeat (MIRU-VNTR) genotyping, and whole-genome sequencing (WGS). The lineage distribution of the MDR-TB isolates comprised 54.7% Euro-American, 33.3% East Asian, 7.2% East African Indian, and 4.8% Indo-Oceanic. A significant association was identified between the East Asian Beijing sub-lineage and the relative risk of an isolate being MDR. Over 75% of MDR-TB cases were confirmed in non-Irish born individuals and 7 MIRU-VNTR genotypes were identical to clusters in other European countries indicating cross-border spread of MDR-TB to Ireland. WGS data provided the first evidence in Ireland of in vivo microevolution of MTBC isolates from drug-susceptible to MDR, and from MDR to extensively-drug resistant (XDR). In addition, they found that the katG S315T isoniazid and rpoB S450L rifampicin resistance mutations were dominant across the different MTBC lineages. Our molecular epidemiological analyses identified the spread of MDR-TB to Ireland from other jurisdictions and its potential to evolve to XDR-TB.