title: Pneumococcal genome sequencing tracks a vaccine escape variant formed through a multi-fragment recombination event.
abstract: Streptococcus pneumoniae ('pneumococcus') causes an estimated 14.5 million cases of serious disease and 826,000 deaths annually in children under 5 years of age(1). The highly effective introduction of the PCV7 pneumococcal vaccine in 2000 in the United States(2,3) provided an unprecedented opportunity to investigate the response of an important pathogen to widespread, vaccine-induced selective pressure. Here, we use array-based sequencing of 62 isolates from a US national monitoring program to study five independent instances of vaccine escape recombination(4), showing the simultaneous transfer of multiple and often large (up to at least 44 kb) DNA fragments. We show that one such new strain quickly became established, spreading from east to west across the United States. These observations clarify the roles of recombination and selection in the population genomics of pneumococcus and provide proof of principle of the considerable value of combining genomic and epidemiological information in the surveillance and enhanced understanding of infectious diseases.
authors.affiliation: Department of Statistics, University of Oxford, UK.
authors.forename: Tanya
authors.initials: T
authors.lastname: Golubchik
authors.forename: Angela B
authors.initials: AB
authors.lastname: Brueggemann
authors.forename: Teresa
authors.initials: T
authors.lastname: Street
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gertz
authors.forename: Chris C A
authors.initials: CC
authors.lastname: Spencer
authors.forename: Thien
authors.initials: T
authors.lastname: Ho
authors.forename: Eleni
authors.initials: E
authors.lastname: Giannoulatou
authors.forename: Ruth
authors.initials: R
authors.lastname: Link-Gelles
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: Harding
authors.forename: Bernard
authors.initials: B
authors.lastname: Beall
authors.forename: Tim E A
authors.initials: TE
authors.lastname: Peto
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Moore
authors.forename: Peter
authors.initials: P
authors.lastname: Donnelly
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.forename: Rory
authors.initials: R
authors.lastname: Bowden
mesh_terms: D001483:Base Sequence; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D056186:Metagenomics; D008969:Molecular Sequence Data; D022242:Pneumococcal Vaccines / Q000235:genetics*; D011014:Pneumonia / Q000453:epidemiology* / Q000382:microbiology*; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: D017931:DNA Primers; D022242:Pneumococcal Vaccines