Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection

Research output: Contribution to journalArticle

Authors

  • Nicholas J Croucher
  • Katherine A Gould
  • Donald Inverarity
  • Lars Barquist
  • Theresa Feltwell
  • Maria C Fookes
  • Simon R Harris
  • Janina Dordel
  • Susannah J Salter
  • Sarah Browall
  • Helena Zemlickova
  • Staffan Normark
  • Birgitta Henriques-Normark
  • Jason Hinds
  • Stephen D Bentley

Colleges, School and Institutes

Abstract

Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex's entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that up-regulated the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through small alterations to the genotype.

Details

Original languageEnglish
Pages (from-to)e1003868
JournalPLoS Genetics
Volume9
Issue number10
Publication statusPublished - 2013

Keywords

  • Animals, Genetic Variation, Genome, Bacterial, High-Throughput Nucleotide Sequencing, Humans, Meningitis, Mice, Mutation, Phylogeny, Serotyping, Streptococcus pneumoniae