Why some strep infections turn deadly: A genetic clue

Osaka, Japan - A group of researchers led by The University of Osaka have identified a novel genetic mutation in Streptococcus pyogenes, a common bacterium which causes strep throat, significantly associated with severe invasive infections. A single mutation in the bacterial ferric ion transporter weakens bacterial growth in human blood. This mutation, unique to Japanese isolates, indicates a novel pathogenic mechanism.  This world-first discovery offers a potential new target for treatments and preventive measures.

S. pyogenes causes severe invasive infections with a high mortality rate. Cases of invasive strep in Japan surged in 2024, highlighting the urgent need for new treatments and a deeper understanding of the underlying disease mechanisms.

A new study looked at the genes of hundreds of S. pyogenes samples from Japan and other countries to pinpoint the genetic differences that make some strains more dangerous. The research group conducted a comprehensive genomic analysis of 666 S. pyogenes strains—311 from Japan and 355 from other countries—using cutting-edge pangenome-wide association studies.

The researchers found a number of genetic changes linked to the bacteria's ability to cause severe infections, including a brand new mutation never seen before. This mutation affects a gene involved in how the bacterium gets iron, a nutrient it needs to survive. Interestingly, they also found that many genes previously thought to cause serious illness were actually common in the less harmful strains. This suggests that some strains may become more dangerous not just by gaining harmful genes, but also by losing genes that hold them back.

This research significantly advances our understanding of severe invasive strep, especially within the Japanese population. "This large-scale analysis, involving painstaking supercomputer analysis and experimental validation, offers a promising avenue for new therapies targeting a mutated iron transporter," explained Dr. Masayuki Ono, the lead author of the study. The study’s pangenome-wide approach also demonstrates the potential of large-scale genomic analyses for unraveling complex disease mechanisms, offering a powerful tool for future research in other infectious diseases.

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The article, “Identifying Genetic Variations in emm89 Streptococcus pyogenes Associated with Severe Invasive Infections,” was published in eLife at DOI: https://doi.org/10.7554/eLife.101938

About The University of Osaka

The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en