Abstract

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single nucleotide polymorphisms (SNPs) and accessory genes as sporadic US Clone 1 isolates. However, pulmonary outbreak isolates were more likely to have AMR mutations compared to sporadic isolates. Clone 1 isolates are present among non-CF and CF patients across the US, but additional studies will be needed to resolve potential routes of transmission and spread.

Highlights

  • Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections

  • This study demonstrates that the M. massiliense dominant Clone 1 is not limited to the respiratory tract of patients with CF, but is found in sporadic wound infections, blood stream infections, and the respiratory tract of primarily older women

  • At the UTHSCT, the prevalence of Clone 1 among all isolates of M. massiliense was surprisingly high compared to the Colorado Research and Development Program (CO-RDP) (39% vs. 17%)

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Summary

Introduction

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. We compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. A genomic analysis of 188 M. massiliense isolates from soft tissue infections across 10 Brazilian states confirmed that the Brazilian strains are closely related to Clone 1 strains from the UK pulmonary o­ utbreak[10]. Genomes than other M. massiliense and contained distinct plasmids called p­ MAB0111 and p­ MAB0210 It is currently unknown if Clone 1 is present among non-CF pulmonary isolates or extrapulmonary infections outside of Brazil. We hypothesize that sporadic US Clone 1 isolates will differ from previously identified outbreak isolates of M. massiliense in terms of genomic similarity and antimicrobial resistance

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