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27 Feb 2023

Genomic research reveals new Strep A variant in Australia

Cases of scarlet fever are on the rise around the globe, with several countries in Europe also reporting an increase in severe invasive Strep A infections. With a similar trend observed in Australia, a team of researchers are staying on top of the curve by conducting genomic surveillance of the bacterium to track its spread.

Scarlet fever is caused by Group A Streptococcus (Strep A), a bacterial pathogen commonly found in the throat and on the skin. While Strep A can cause common infections such as sore throat, scarlet fever and impetigo, in some rare cases, the bacteria can also lead to severe, life-threatening infections known as invasive group A Streptococcus diseases (iGAS), like sepsis or toxic-shock syndrome.

The surge in cases in the UK has been associated with a new variant of the Strep A bacterium called M1uk, which quickly took over from the original strain. For the first time and thanks to genomic surveillance, scientists have discovered the same variant is now circulating in Australia too.

In the study published in Nature Communications, researchers from The Peter Doherty Institute for Immunity and Infection (Doherty Institute) and The University of Queensland's Institute for Molecular Bioscience reported the detection of this particular strain of Strep A M1uk in Australia and discovered what makes this variant markedly different to the original bacterium.

Earlier studies showed that the new M1uk variant exhibits an enhanced expression of one particular virulence toxin which subverts the immune system. How this change took place and what its genetic features are had remained a mystery, until this team of Australian scientists unlocked its secret.

University of Melbourne’s Dr Mark Davies is a Senior Lecturer in Bacteriology and Laboratory Head in the Department of Microbiology and Immunology at the Doherty Institute, and co-lead author of this study.

“Through genomic surveillance, we were able to detect the presence and unappreciated expansion of this new Strep A variant within Queensland and Victorian public health settings.”

“We undertook an extensive laboratory analysis with our colleagues at The University of Queensland, to characterise the mechanism by how this toxin has been upregulated and understand how the bug is changing,” Dr Davies said.

“So, through a process of elimination we identified that enhanced toxin expression was associated with a single mutation in a bacterial gene near the toxin. This mutation results in ineffective termination of gene transcription leading to elevated levels of the neighbouring toxin gene.” 

Professor Mark Walker from The University of Queensland said that while understanding the mechanism of how this new variant upregulates this toxin is a leap forward, we are still characterising why we're seeing an upsurge in cases.

“We need to monitor this variant to find out whether it is directly linked with the clinical increase of cases or not. To do this, we need to have enhanced genomic surveillance for this new M1uk variant,” Professor Walker said.

“Together with Dr Davies and his team and our other clinical and public health collaborators in Queensland and Victoria, we are continuing to provide genomic surveillance of Strep A. We’ve been undertaking sentinel surveillance for disease causing Strep A strains since 2012. Now that iGAS has been made notifiable nationally, we will be able to monitor its spread around Australia.”

“Our research shows a new pattern of toxin expression and urges enhanced international surveillance,” Dr Davies added.

This work is the result of extensive collaboration across Victoria and Queensland that have involved research labs and clinical public health labs.

Professor Ben Howden, Director of Microbiological Diagnostic Unit Public Health Laboratory at the Doherty Institute, remarked that this project highlights the value of using genomic data to enhance the surveillance of infectious diseases.

“As we use genomics more routinely in public health microbiology, it will improve our ability to detect and respond to emerging threats such as this Strep A variant. We are currently integrating iGAS into a national genomic surveillance program, termed AusPathoGen, a government-funded initiative that supports genomic surveillance of notifiable pathogens, which will expediate our ability to detect problem variants” Professor Howden said.

The partnership between the Doherty Institute and the University of Queensland researchers has recently been recognised with a philanthropic grant from the Leducq Foundation to support the development of an mRNA vaccine to reduce Strep A infections worldwide.

Peer-review: Nature Communications
Funding: National Health and Medical Research Council (NHMRC).