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bioRxiv · 10.1101/2024.07.02.601674

Identifying Genetic Variations in emm89 Streptococcus pyogenes Linked to Severe Invasive Infections

Ono, M.·Yamaguchi, M.·Motooka, D.·Hirose, Y.·Higashi, K.·Sumitomo, T.·Miyoshi-Akiyama, T.·Okuno, R.·Yamaguchi, T.·Kawahara, R.·Otsuka, H.·Nakanishi, N.·Kazawa, Y.·Nakagawa, C.·Yamaguchi, R.·Sakai, H.·Matsumoto, Y.·Ikebe, T.·Kawabata, S.
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Abstract

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 emm89 S. pyogenes strains to comprehensively identify pathology-related bacterial genetic factors (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 1,075 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 emm89 S. pyogenes to an invasive phenotype and a platform for establishing novel treatments and prevention strategies.

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Ono, M., Yamaguchi, M., Motooka, D., Hirose, Y., Higashi, K., Sumitomo, T., Miyoshi-Akiyama, T., Okuno, R., Yamaguchi, T., Kawahara, R., Otsuka, H., Nakanishi, N., Kazawa, Y., Nakagawa, C., Yamaguchi, R., Sakai, H., Matsumoto, Y., Ikebe, T., Kawabata, S.. 2024-07-02. Identifying Genetic Variations in emm89 Streptococcus pyogenes Linked to Severe Invasive Infections. https://doi.org/10.1101/2024.07.02.601674

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