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Identifying genetic drivers of Streptococcus pyogenes

This project is focused on identifying genetic drivers of Streptococcus pyogenes isolated from children in Aotearoa New Zealand to better understand disease causality.

Streptococcus pyogenes presents a serious human health problem. Group A Streptococcus (GAS or Streptococcus pyogenes) is responsible for more than 600 million cases per year worldwide. In Aotearoa, it disproportionately impacts Pacific peoples and Māori, with significant proportions of children affected. GAS infections can lead to a wide variety of clinical outcomes, from minor to serious disease (such as rheumatic heart disease).

The research aim is to better understand how very similar bacteria can have hugely different outcomes, ranging from asymptomatic carriage to minor infections to severe disease, which are not fully explained by environmental and host factors. Currently, we do not fully understand the genetic drivers associated with the clinical manifestation. There is a complex relationship between genotype and phenotype in bacterial pathogens, where phenotypic features such as invasiveness or resistance to antimicrobials are difficult to predict from genomes.

The first project step is proof of concept, deploying a species agnostic model, applying a machine learning approach. The second step is a detailed study of the population genomics of Streptococcus pyogenes in Aotearoa. The analysis allows us to identify genetically similar isolates with known differences in clinical symptoms. These isolates will be used in a third step to develop a model to identify likely genetic candidates that correlate with particular phenotypes or outcomes.

Team

  • Joep de Ligt, ESR, co-leader
  • Paul Gardner, University of Otago, co-leader
  • Christina Straub, ESR
  • Julie Bennett, University of Otago
  • Nigel French, Massey University
  • Una Ren, ESR