Clin Infect Dis. 2016 Feb 7. pii: ciw050. [Epub ahead of print]

Whole-Genome Sequencing Reveals the Origin and Rapid Evolution of an Emerging Outbreak Strain ofStreptococcus pneumoniae 12F.

Deng X1, Peirano G2, Schillberg E3, Mazzulli T1, Gray-Owen SD4, Wylie JL5, Robinson DA6, Mahmud SM7, Pillai DR8.

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 Streptococcus pneumoniae is 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.


 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.


 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 harboring msrD and mefE. Furthermore, during 11 months of transmission, this clone evolved rapidly and acquired fluoroquinolone resistance through precise stepwise mutations in both parC and gyrA, and putative compensatory mutations in uraA or IMPDH under 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.


 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.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail


12F; ST218; Streptococcus pneumoniae; pneumococcal outbreaks; whole-genome sequencing

PMID: 26908785 [PubMed - as supplied by publisher]