title: Whole-genome sequencing and epidemiological analysis do not provide evidence for cross-transmission of mycobacterium abscessus in a cohort of pediatric cystic fibrosis patients.
abstract: BACKGROUND
  Mycobacterium abscessus has emerged as a major pathogen in cystic fibrosis (CF) patients and has been associated with poor clinical outcomes, particularly following lung transplant. We investigated the acquisition of this bacterium in a cohort of pediatric CF patients.
  
  
  METHODS
  Demographic and patient location data were used to uncover epidemiological links between patients with genetically related strains of M. abscessus that had been previously typed by variable-number tandem repeat profiling. Whole-genome sequencing was applied to 27 M. abscessus isolates from the 20 patients in this cohort to provide definitive data on the genetic relatedness of strains.
  
  
  RESULTS
  Whole-genome sequencing data demonstrated that M. abscessus isolates from 16 patients were unrelated, differing by at least 34 single-nucleotide polymorphisms (SNPs) from any other isolate, suggesting that independent acquisition events have occurred. Only 2 clusters of very closely related (<25 SNPs) isolates from different patients were seen. The first cluster contained 8 isolates, differing by a maximum of 17 SNPs, from a sibling pair who had intense exposure to each other both inside and outside the hospital. The second cluster contained 3 isolates, differing by a maximum of 24 SNPs, from 2 individuals with no apparent epidemiological links.
  
  
  CONCLUSIONS
  We have not demonstrated cross-transmission of M. abscessus within our hospital, except between 1 sibling pair. Alternative routes of acquisition of M. abscessus infection, in particular the environment, require further investigation.
authors.affiliation: Department of Microbiology, Virology and Infection Control, Great Ormond Street Hospital NHS Foundation Trust National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Harris
authors.affiliation: Bioinformatics Unit, Infectious Disease Informatics, Microbiology Services (Colindale), Public Health England.
authors.forename: Anthony
authors.initials: A
authors.lastname: Underwood
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Reference Microbiology Services, Public Health England.
authors.forename: Dervla T D
authors.initials: DT
authors.lastname: Kenna
authors.affiliation: UCL Genomics, University College London, Institute of Child Health.
authors.forename: Anthony
authors.initials: A
authors.lastname: Brooks
authors.affiliation: Paediatric Respiratory Medicine and Lung Transplantation, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Ema
authors.initials: E
authors.lastname: Kavaliunaite
authors.affiliation: Bioinformatics Unit, Infectious Disease Informatics, Microbiology Services (Colindale), Public Health England.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kapatai
authors.affiliation: Bioinformatics Unit, Infectious Disease Informatics, Microbiology Services (Colindale), Public Health England.
authors.forename: Rediat
authors.initials: R
authors.lastname: Tewolde
authors.affiliation: Paediatric Respiratory Medicine and Lung Transplantation, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Aurora
authors.affiliation: Department of Microbiology, Virology and Infection Control, Great Ormond Street Hospital NHS Foundation Trust National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
authors.forename: Garth
authors.initials: G
authors.lastname: Dixon
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications*; D004812:Epidemiologic Methods; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D008297:Male; D058889:Molecular Typing; D009161:Mycobacterium / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D009165:Mycobacterium Infections, Nontuberculous / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D017385:Sequence Homology
keywords: Mycobacterium abscessus; VNTR; cross-transmission; cystic fibrosis; whole-genome sequencing