New Strep A variant: research urges enhanced international surveillance

The surge in scarlet fever cases in the UK has been associated with a new variant of the Strep A bacterium called M1uk. Genomic surveillance has discovered the same variant is now circulating in Australia too.

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.

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 that 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.

The 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,” 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, they are still investigating why there has been 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,” 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,” Davies added.

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 expedite our ability to detect problem variants” 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.

Image credit: iStock.com/JUN LI