Population Genomics of Mycobacterium abscessus from United States Cystic Fibrosis Care Centers.

RationaleMycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) due to innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States (US). Objectives We examined the genetic diversity of respiratory M. abscessus isolates from US patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods Whole genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 US states as part of a nationwide surveillance program. US isolates were also compared to 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subsp. abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared to unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (p=1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28/204 (14%) patients with MAB and 15/64 (23%) with MMAS had genetically similar isolates to at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60/204 (29%) patients with MAB and 19/64 (30%) with MMAS from different geographic locations. Conclusions Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in US CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the US, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of healthcare-associated transmission versus shared environmental exposures.