Frequency-dependent selection can forecast evolution in Streptococcus pneumoniae

Taj Azarian, Pamela P. Martinez, Brian J. Arnold, Xueting Qiu, Lindsay R. Grant, Jukka Corander, Christophe Fraser, Nicholas J. Croucher, Laura L. Hammitt, Raymond Reid, Mathuram Santosham, Robert C. Weatherholtz, Stephen D. Bentley, Katherine L. O’Brien, Marc Lipsitch, William P. Hanage

Research output: Contribution to journalArticlepeer-review


Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain, estimated by an NFDS-based model at the time the vaccine is introduced, enables us to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.

Original languageEnglish (US)
Article numbere3000878
JournalPLoS biology
Issue number10
StatePublished - Oct 22 2020
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


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