Abstract
Rapidly growing, non-tuberculous mycobacteria (NTM) in the Mycobacterium abscessus (MAB) species are emerging pathogens that cause various diseases including skin and respiratory infections. The species has undergone recent taxonomic nomenclature refinement, and is currently recognized as two subspecies, M. abscessus subsp. abscessus (MAB-A) and M. abscessus subsp. bolletii (MAB-B). The recently reported outbreaks of MAB-B in surgical patients in Brazil from 2004 to 2009 and in cystic fibrosis patients in the United Kingdom (UK) in 2006 to 2012 underscore the need to investigate the genetic diversity of clinical MAB strains. To this end, we sequenced the genomes of two Brazilian MAB-B epidemic isolates (CRM-0019 and CRM-0020) derived from an outbreak of skin infections in Rio de Janeiro, two unrelated MAB strains from patients with pulmonary infections in the United States (US) (NJH8 and NJH11) and one type MAB-B strain (CCUG 48898) and compared them to 25 publically available genomes of globally diverse MAB strains. Genome-wide analyses of 27,598 core genome single nucleotide polymorphisms (SNPs) revealed that the two Brazilian derived CRM strains are nearly indistinguishable from one another and are more closely related to UK outbreak isolates infecting CF patients than to strains from the US, Malaysia or France. Comparative genomic analyses of six closely related outbreak strains revealed geographic-specific large-scale insertion/deletion variation that corresponds to bacteriophage insertions and recombination hotspots. Our study integrates new genome sequence data with existing genomic information to explore the global diversity of infectious M. abscessus isolates and to compare clinically relevant outbreak strains from different continents.
Highlights
Growing, nontuberculous mycobacteria (NTM) species are opportunistic pathogens that cause a range of diseases including lung (Griffith, 2010) and skin (Khan and Khakoo, 2011) infections, and are thought to be primarily acquired from the environment (Primm et al, 2004)
Two additional strains were isolated from the sputa of United States (US) patients referred to National Jewish Health in Denver, CO, including NJH8 that was derived from a patient with a pulmonary NTM infection in 2011 and was identified as Mycobacterium abscessus (MAB)-A by rpoB sequencing, and NJH11 that was derived from a patient with cystic fibrosis and a pulmonary NTM infection in 2009, and was identified as M. abscessus subsp. bolletii (MAB-B) by rpoB sequencing
A majority of single nucleotide polymorphisms (SNPs) vary within MAB-B (22,882/27,598=82.9%) compared to the SNP variation observed within M. abscessus subsp. abscessus (MAB-A) (3,507/27,598=12.7%)
Summary
Nontuberculous mycobacteria (NTM) species are opportunistic pathogens that cause a range of diseases including lung (Griffith, 2010) and skin (Khan and Khakoo, 2011) infections, and are thought to be primarily acquired from the environment (Primm et al, 2004). Several outbreaks of post-surgical infections caused by a subtype of Mycobacterium abscessus were reported in various regions of Brazil from 2004 to 2009 (Cardoso et al, 2008; Duarte et al, 2009; Monego et al, 2011; Viana-Niero et al, 2008) These emerging Brazilian outbreak strains were thought to be related to the selection and spread of a virulent epidemic isolate named BRA100, showing a high level of resistance to glutaraldehyde (GTA), the disinfectant used in hospital sites that had reported cases (Duarte et al, 2009; Leao et al, 2009; Shang et al, 2011). Whether differences in the colonial morphotype of BRA100 isolates relative to CIP108297 (Shang et al, 2011) and, cell envelope lipid composition (Howard et al, 2006) may account for this difference in pathogenicity is currently under investigation
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