Identifying Genetic Variations in emm89 Streptococcus pyogenes Associated with Severe Invasive Infections

• DOI: 10.7554/elife.101938.2
• Publication Date: 2025-05-20T15:30:08Z
• Authors: Masayuki Ono; Masaya Yamaguchi; Daisuke Motooka; Yujiro Hirose; Kotaro Higashi; Tomoko Sumitomo; Tohru Miyoshi-Aki...; Rumi Okuno; Takahiro Yamaguchi; Ryuji Kawahara; Hitoshi Otsuka; Noriko Nakanishi; Yu Kazawa; Chikara Nakagawa; Ryo Yamaguchi; Hiroo Sakai; Yuko Matsumoto; Tadayoshi Ikebe; Shigetada Kawabata
• Keywords: Streptococcus Pyogenes; STREPTOCOCCAL INFECTIONS

Abstract Streptococcus pyogenes causes mild human infections as well life-threatening invasive diseases. Since the mutations known to enhance virulence date account for only half of severe infections, additional mechanisms/mutations need be identified. Here, we conducted a genome-wide association study emm89 S. strains comprehensively identify pathology-related bacterial genetic factors (SNPs, indels, genes, or k-mers). Japanese (n=311) and global (n=666) cohort studies isolated from non-invasive revealed 17 1,075 SNPs/indels 2 169 respectively, that displayed associations with invasiveness. We validated one them, non-invasiveness-related point mutation, fhuB T218C, by structure predictions introducing it into strain confirmed mutant showed slower growth in blood. Thus, report novel mechanisms convert an phenotype platform establishing treatments prevention strategies.