title: Genome sequencing of Mycobacterium abscessus isolates from patients in the united states and comparisons to globally diverse clinical strains.
abstract: 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.
authors: Integrated Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA.
authors: Rebecca M
authors: RM
authors: Davidson
authors: Integrated Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA Computational Bioscience Program, University of Colorado Denver, School of Medicine, Aurora, Colorado, USA.
authors: Nabeeh A
authors: NA
authors: Hasan
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
authors: Paul R
authors: PR
authors: Reynolds
authors: Mycobacteriology and Pharmacokinetics, National Jewish Health, Denver, Colorado, USA.
authors: Sarah
authors: S
authors: Totten
authors: Integrated Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA Computational Bioscience Program, University of Colorado Denver, School of Medicine, Aurora, Colorado, USA.
authors: Benjamin
authors: B
authors: Garcia
authors: Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, Colorado, USA.
authors: Adrah
authors: A
authors: Levin
authors: Department of Academic Affairs, National Jewish Health, Denver, Colorado, USA.
authors: Preveen
authors: P
authors: Ramamoorthy
authors: Mycobacteriology and Pharmacokinetics, National Jewish Health, Denver, Colorado, USA.
authors: Leonid
authors: L
authors: Heifets
authors: Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, Colorado, USA.
authors: Charles L
authors: CL
authors: Daley
authors: Integrated Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA Computational Bioscience Program, University of Colorado Denver, School of Medicine, Aurora, Colorado, USA strongm@njhealth.org.
authors: Michael
authors: M
authors: Strong
mesh_terms: D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014481:United States