Genome Sequencing of Mycobacterium abscessus Isolates from Patients in the United States and Comparisons to Globally Diverse Clinical Strains

Abstract

f Nontuberculous mycobacterial infections caused by Mycobacterium abscessus are responsible for a range of disease manifestations from pulmonary to skin infections and are notoriously difficult to treat, due to innate resistance to many antibiotics. Previous population studies of clinical M. abscessus isolates utilized multilocus sequence typing or pulsed-field gel electrophoresis, but high-resolution examinations of genetic diversity at the whole-genome level have not been well characterized, particularly among clinical isolates derived in the United States. We performed whole-genome sequencing of 11 clinical M. abscessus isolates derived from eight U.S. patients with pulmonary nontuberculous mycobacterial infections, compared them to 30 globally diverse clinical isolates, and investigated intrapatient genomic diversity and evolution. Phylogenomic analyses revealed a cluster of closely related U.S. and Western European M. abscessus subsp. abscessus isolates that are genetically distinct from other European isolates and all Asian isolates. Large-scale variation analyses suggested genome content differences of 0.3 to 8.3%, relative to the reference strain ATCC 19977 T . Longitudinally sampled isolates showed very few single-nucleotide polymorphisms and correlated genomic deletion patterns, suggesting homogeneous infection populations. Our study explores the genomic diversity of clinical M. abscessus strains from multiple continents and provides insight into the genome plasticity of an opportunistic pathogen. N ontuberculous mycobacteria (NTM) represent a diverse group of environmental and pathogenic bacteria that are increasing in clinical prevalence in the United States (1) and other countries (2, 3). NTM are thought to be acquired primarily through environmental exposure (4), as they reside in water, biofilms, and soil environments (5, 6), although a few recent studies provide evidence of possible person-to person transmission among individuals with cystic fibrosis (CF) (7,8). Mycobacterium abscessus is the second most clinically prevalent NTM species in pulmonary NTM infections (1, 9, 10), with Mycobacterium avium complex (MAC) being the most prevalent. M. abscessus infections are challenging to treat because they are innately resistant to many antimicrobials, including some that are effective against Mycobacterium tuberculosis and other mycobacteria (11-13). Acquired antibiotic resistance has been observed in some M. abscessus strains, with mechanisms of resistance ranging from mutational resistance to aminoglycosides (14) to mutational (15) and inducible (16) resistance to macrolides.The current taxonomy of M. abscessus recognizes two subspecies, M. abscessus subsp. abscessus and M. abscessus subsp. bolletii (17), although recent population and comparative genomic studies support the three previously recognized subspecies, i.e., M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii (18)(19)(20)(21). This delineation is important because clinical studies suggest diff...

Molecular epidemiology of Mycobacterium abscessus complex isolates in Ireland

“…abscessus) and tight clusters of horizontally transmitted strains acquired from other patients (M. abscessus subsp. massiliense) [9,34]. The requirement for multiple sequence targets to correctly assign strains to M. abscessus subsp.…”

Evaluation of Matrix-Assisted Laser Desorption Ionization−Time of Flight Mass Spectrometry for Identification of Mycobacterium abscessus Subspecies According to Whole-Genome Sequencing

“…abscessus isolates collected in Europe and the United States revealed unique peak patterns, i.e., specific signals at 2,081 m/z and 3,378 m/z (23,24). Possibly these occurred as a function of horizontal gene transfer and genetic background differences that influence the evolution of M. abscessus worldwide (35,49). This possibility concurs with the fact that our profiles are similar to others found in Asia but diverge from those found in Europe and the United States (25)(26)(27).…”

“…massiliense), and CIP108541 (M. abscessus subsp. bolletii) served as reference controls (11,14,34,35). H37Rv (M. tuberculosis) was used as a separate species reference control.…”

Molecular mechanisms of clarithromycin resistance in Mycobacterium abscessus complex clinical isolates from Venezuela

“…The polymorphisms found in the erm(41) gene sequences in the different species studied indicate that these microorganisms are a heterogeneous group with a high genetic diversity, which may be related to specific geographic areas [27,28].…”