title: Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine.
abstract: Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.
authors.affiliation: Centre for Systems Biology, School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Loman
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Gladstone
authors.forename: Chrystala
authors.initials: C
authors.lastname: Constantinidou
authors.forename: Anna S
authors.initials: AS
authors.lastname: Tocheva
authors.forename: Johanna M C
authors.initials: JM
authors.lastname: Jefferies
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.forename: Leigh
authors.initials: L
authors.lastname: O'Connor
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chan
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Clarke
mesh_terms: D049109:Cell Proliferation; D002999:Clone Cells; D056426:Genetic Loci / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D010802:Phylogeny; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000166:cytology / Q000235:genetics / Q000276:immunology*
chemical_list: D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines