Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Ouli Xie, Jacqueline M. Morris, Andrew J. Hayes, Rebecca J. Towers, Magnus G. Jespersen, John A. Lees, Nouri L. Ben Zakour, Olga Berking, Sarah L. Baines, Glen P. Carter, Gerry Tonkin-Hill, Layla Schrieber, Liam McIntyre, Jake A. Lacey, Taylah B. James, Kadaba S. Sriprakash, Scott A. Beatson, Tadao Hasegawa, Phil Giffard, Andrew C. SteerMichael R. Batzloff, Bernard W. Beall, Marcos D. Pinho, Mario Ramirez, Debra E. Bessen, Gordon Dougan, Stephen D. Bentley, Mark J. Walker, Bart J. Currie, Steven Y.C. Tong, David J. McMillan, Mark R. Davies

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Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

Original languageEnglish
Article number2286
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2024

Bibliographical note

Funding Information:
The authors would like to acknowledge that a portion of samples were collected from Aboriginal Australian populations which are severely impacted by streptococcal associated disease, and we hope that this study can add to the evidence base assisting in the prevention of such diseases. The work was supported by the National Health and Medical Research Council of Australia (NHMRC) and The Wellcome Trust, UK. MRD was supported by a NHMRC postdoctoral training fellowship (635250) and a University of Melbourne CR Roper Fellowship. OX was supported by the NHMRC postgraduate scholarship (GNT2013831) and Avant Foundation Doctors in Training Research Scholarship (2021/000017). We acknowledge the assistance of the sequencing and pathogen informatics core teams at the Wellcome Sanger Institute, UK where this work was supported by the Wellcome Trust core grants 206194 and 108413/A/15/D.

Publisher Copyright:
© The Author(s) 2024.


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