Whole-Genome Sequencing and Epidemiological Analysis Do Not Provide Evidence for Cross-transmission of Mycobacterium abscessus in a Cohort of Pediatric Cystic Fibrosis Patients

Mycobacterium abscessus has emerged as a major pathogen in cystic fibrosis (CF) patients and has been associated with poor clinical outcomes, particularly following lung transplant [1–3]. Mycobacterium abscessus is resistant to most classes of antibiotics [4, 5]. Macrolide resistance is either due to mutations in the rrl gene or the presence of an inducible ribosomal RNA methylase gene, erm(41) [6–8]. Mycobacterium abscessus is a single species that encompasses 3 subspecies (M. abscessus subsp abscessus, M. abscessus subsp massiliense, and M. abscessus subsp bolletii) [8–11]. These 3 subspecies have been associated with varying clinical outcomes [8, 12–14]. Accurate identification can generally be achieved by sequencing multiple gene targets [15]. Variable-number tandem repeat (VNTR) profiling can further differentiate isolates [9, 16] and, when applied to our cohort, showed that the majority of chronically infected patients were infected with 1 of 2 dominant strains. [9]. Whole-genome sequencing can provide more definitive data on the relatedness of isolates. Several publications have reported whole-genome sequences from a single M. abscessus complex isolate [17–20] or several isolates from a single patient [21]. Whole-genome sequences of M. abscessus subsp massiliense isolates from a cohort of adults with CF provided the first evidence that patient-to-patient spread can occur [10]. We describe the dynamics of acquisition of M. abscessus in a cohort of pediatric CF patients, using epidemiological and clinical data to uncover evidence of cross-transmission events and whole-genome sequencing to establish the resolution of the previously published VNTR typing scheme. Ultimately, this will lead to a better understanding of the impact of particular strains on clinical outcomes, especially following lung transplant.