Identifying genetic variations in emm89 Streptococcus pyogenes associated with severe invasive infections
Streptococcus pyogenes causes mild human infections as well as life-threatening invasive diseases. Since the mutations known to enhance virulence to date account for only half of the severe invasive infections, additional mechanisms/mutations need to be identified. Here, we conducted a genome-wide association study of emm 89 S. pyogenes strains to comprehensively identify pathology-related bacterial genetic factors (single-nucleotide polymorphisms [SNPs], indels, genes, or k-mers). Japanese ( n = 311) and global ( n = 666) cohort studies of strains isolated from invasive or non-invasive infections revealed 17 and 1075 SNPs/indels and 2 and 169 genes, respectively, that displayed associations with invasiveness. We validated one of them, a non-invasiveness-related point mutation, fhuB T218C, by structure predictions and introducing it into a severe invasive strain and confirmed that the mutant showed slower growth in human blood. Thus, we report novel mechanisms that convert emm 89 S. pyogenes to an invasive phenotype and a platform for establishing novel treatments and prevention strategies.
Authors
- Daisuke Motooka (ORCID: https://orcid.org/0000-0002-4616-9608)
- Hiroo Sakai
- M. Yamaguchi (ORCID: https://orcid.org/0000-0001-6218-7112)
- Shigetada Kawabata (ORCID: https://orcid.org/0009-0005-1660-9544)
- Ryuji Kawahara (ORCID: https://orcid.org/0000-0002-6864-3788)
- Tadayoshi Ikebe (ORCID: https://orcid.org/0000-0003-1021-1728)
- Takahiro Yamaguchi (ORCID: https://orcid.org/0000-0001-9296-0348)
- Yu Kazawa
- Yujiro Hirose (ORCID: https://orcid.org/0000-0001-6338-4767)
- Noriko Nakanishi (ORCID: https://orcid.org/0000-0002-3088-1254)
- Tohru Miyoshi‐Akiyama (ORCID: https://orcid.org/0000-0003-1838-0825)
- Hitoshi Otsuka
- Chikara Nakagawa
- Rumi Okuno
- Tomoko Sumitomo (ORCID: https://orcid.org/0000-0003-0653-0339)
- Ryo Yamaguchi (ORCID: https://orcid.org/0000-0003-2012-0299)
- Kotaro Higashi (ORCID: https://orcid.org/0000-0001-9529-1557)
- M. Ono (ORCID: https://orcid.org/0009-0006-9557-9669)
- Yuko Matsumoto
Institutions
- National Institute of Infectious Diseases (JP)
- National Institute of Biomedical Innovation, Health and Nutrition (JP)
- Institute of Public Health (AL)
- National Center for Global Health and Medicine (JP)
- Tokyo Metropolitan Institute of Public Health (JP)
- Fukushima Prefectural Culture Center (JP)
- Center for Global Health (US)
- Yamagata Prefectural Institute of Public Health (JP)
- Osaka International Cancer Institute (JP)
- Kyoto Prefectural Institute of Public Health and Environment (JP)
- Tokushima University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- eLife
- Published
- 2025-07-24
- DOI
- https://doi.org/10.7554/elife.101938.3
- Primary Topic
- Streptococcal Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science