title: Whole-Genome Sequencing Reveals the Origin and Rapid Evolution of an Emerging Outbreak Strain of Streptococcus pneumoniae 12F.
abstract: BACKGROUND
  Streptococcus pneumoniaeis a major cause of community-acquired pneumonia and septicemia in adults. The global drug-susceptible capsular serotype 12F, clonal complex 218 caused several outbreaks in the United States between 1989 and 2008, as well as a recent large outbreak in Manitoba, Canada, that resulted in 36 cases of septicemia and 3 deaths. The evolutionary origin of the Canadian outbreak strain and its relationship to the historical US outbreak strains are not known.
  
  
  METHODS
  Whole-genome deep sequencing was performed on isolates from the Canadian outbreak (n = 36), the US outbreaks (n = 9), and nonoutbreak surveys (n = 21). Phylogenomic analysis and comparative genomics were used to assess evolutionary relationships and to detect gene content differences between the isolates.
  
  
  RESULTS
  The Canadian outbreak was closely related to sporadic cases that occurred preoutbreak in cross-border geographic regions in Manitoba, North Dakota, and Iowa. The emerging Canadian strain differed from US strains by acquisition of a cell-surface protein and macrolide resistance determinants via incorporation of a 5.3-kb mega cassette harboringmsrDandmefE Furthermore, during 11 months of transmission, this clone evolved rapidly and acquired fluoroquinolone resistance through precise stepwise mutations in bothparCandgyrA, and putative compensatory mutations inuraAorIMPDHunder drug selection. Alarmingly, this drug-resistant clone appears to have spread quickly to other regions of Canada and the United States, and replaced drug-susceptible strains.
  
  
  CONCLUSIONS
  Whole-genome sequencing revealed an independent emergence and secondary adaptation of a new virulent and drug-resistant pneumococcal epidemic clone. Ongoing molecular surveillance is required, and measures to prevent its spread should be developed.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto.|Department of Microbiology and Immunology, University Health Network/Mount Sinai Hospital, Toronto.
authors.forename: Xianding
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Calgary.
authors.forename: Gisele
authors.initials: G
authors.lastname: Peirano
authors.affiliation: Winnipeg Regional Health Authority.
authors.forename: Erin
authors.initials: E
authors.lastname: Schillberg
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto.|Department of Microbiology and Immunology, University Health Network/Mount Sinai Hospital, Toronto.
authors.forename: Tony
authors.initials: T
authors.lastname: Mazzulli
authors.affiliation: Department of Molecular Genetics, University of Toronto.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gray-Owen
authors.affiliation: Cadham Provincial Laboratory, Winnipeg, Canada.
authors.forename: John L
authors.initials: JL
authors.lastname: Wylie
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson.
authors.forename: D Ashley
authors.initials: DA
authors.lastname: Robinson
authors.affiliation: Vaccine and Drug Evaluation Centre, Faculty of Health Sciences, University of Manitoba, Winnipeg.
authors.forename: Salaheddin M
authors.initials: SM
authors.lastname: Mahmud
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Calgary.|Calgary Laboratory Services, Canada.
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Pillai
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D005075:Biological Evolution; D002170:Canada; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D016680:Genome, Bacterial; D006801:Humans; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000235:genetics; D017422:Sequence Analysis, DNA; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics*; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents
keywords: 12F; ST218; Streptococcus pneumoniae; pneumococcal outbreaks; whole-genome sequencing