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Doherty Institute researchers have uncovered groundbreaking insights into the genetic similarities and overlap between Streptococcus pyogenes (Strep A) and emerging pathogen Streptococcus dysgalactiae subsp. equisimilis (SDSE), challenging previous assumptions about their relationship.

Previously deemed relatively harmless, SDSE has now emerged as a clinically significant bacterial pathogen, causing severe invasive infections in adults globally. Despite being historically regarded as less virulent than Strep A, serious SDSE infections are becoming more frequent, with clinical presentations resembling those of Strep A infections. These range from mild conditions, including tonsillitis or minor skin infections, to life-threating conditions, such as flesh-eating infections or streptococcal toxic shock syndrome.

Using cutting-edge genomics combined with real-world clinical data collected in partnership with global collaborators – an approach called population genomics – researchers explored how SDSE and Strep A interact and evolve together.

The world-first research, published across two papers in Nature Communications, revealed that SDSE and Strep A not only coexist but also share genes, therefore sharing potential vaccine targets.

The University of Melbourne’s Dr Ouli Xie, an Infectious Diseases Physician undertaking a clinical PhD at the Doherty Institute and first author of both papers, said the findings showed that rather than interfering with each other, SDSE and Strep A evolve with each other, like "two tango dancers".

“We’ve discovered that SDSE and Strep A have a lot more in common genetically than what was previously thought,” said Dr Xie.

“Our findings showed genetic and transmission overlap between the two pathogens, with the bacteria sharing many genes, including those thought to be important for causing disease and antibiotic resistance to a much greater extent than previously appreciated.”

The researchers also found that many genes targeted by Strep A vaccine candidates in development are present in SDSE, with some genes showing mixed characteristics from both species.

The Royal Melbourne Hospital’s Professor Steven Tong, Infectious Diseases Physician with the Victorian Infectious Diseases Service at the Doherty Institute and co-lead author of the papers, said the cross-species interactions suggested in the findings should be considered in the design of Strep A vaccines in development.

“The discovery of shared vaccine targets between SDSE and Strep A could inform the development of future vaccines that combat both pathogens simultaneously, offering broader protection against streptococcal infections,” said Professor Tong.

“We hope that our findings will inform preventative strategies against streptococcal diseases, such as vaccine design.”

Dr Josh Osowicki, a leading researcher on streptococcal disease at the Murdoch Children's Research Institute (MCRI), said he is optimistic about what this research could mean for cellulitis, a common and often painful bacterial skin infection that can escalate into a serious condition if left untreated.

“These studies suggest that many Strep A vaccine candidates in development could also protect against SDSE infections,” said Dr Osowicki.

“Together, Strep A and SDSE are very common causes of cellulitis at all ages. As well as preventing strep throat, life-threatening sepsis and rheumatic heart disease, these could be cellulitis vaccines.”

The University of Melbourne’s Dr Mark Davies, Laboratory Head at the Doherty Institute and co-lead author of the papers, said that the findings highlight a need to expand surveillance of SDSE.

“There is a knowledge gap about how organisms interact with each other, and although there has been a lot of attention on Strep A disease recently, SDSE should not be ignored,” said Dr Davies.

“Our research underscores the importance of improving SDSE disease surveillance and gaining better understanding of the burden of SDSE disease in Australia. In parallel, we aim to delve deeper into the shared biology of the two pathogens to inform the development of vaccine candidates to tackle the two organisms.

“This discovery fundamentally shifts our understanding of these bacteria and their potential impact on human health.”

Peer review: 

• Xie O, et al. Inter-species gene flow drives ongoing Evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis. Nature Communications (2024). https://doi.org/10.1038/s41467-024-46530-2
   
• Xie O, et al. Overlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange. Nature Communications (2024).  https://doi.org/10.1038/s41467-024-47816-1

Collaborators: Charles Darwin University, University of Queensland, University of Oslo, The University of Sydney, QIMR Berghofer Medical Research Institute, Nagoya City University Graduate School of Medical Sciences, Murdoch Children’s Research Institute, Centers for Disease Control and Prevention, Universidade de Lisboa, New York Medical College, Wellcome Sanger Institute, University of the Sunshine Coast, James Cook University, Telethon Kids Institute,

Funding: NHMRC, Wellcome Trust, UK Avant Foundation Doctors in Training Research Scholarship, Wellcome Sanger Institute.