title: Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E Pneumococci.
abstract: The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: van Tonder
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Bray
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Roalfe
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: White
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Zancolli
authors.affiliation: University of Iceland, Reykjavik, Iceland Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Sigríður J
authors.initials: SJ
authors.lastname: Quirk
authors.affiliation: University of Iceland, Reykjavik, Iceland Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Gunnsteinn
authors.initials: G
authors.lastname: Haraldsson
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: University of Iceland, Reykjavik, Iceland Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Ásgeir
authors.initials: Á
authors.lastname: Haraldsson
authors.affiliation: University of Iceland, Reykjavik, Iceland Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Helga
authors.initials: H
authors.lastname: Erlendsdóttir
authors.affiliation: University of Iceland, Reykjavik, Iceland Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Kristinsson
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom angela.brueggemann@ndm.ox.ac.uk.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Brueggemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001770:Blood Bactericidal Activity; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D014943:Global Health; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000276:immunology; D015995:Prevalence; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D055815:Young Adult
chemical_list: D022242:Pneumococcal Vaccines