Identifying Genetic Variations inemm89Streptococcus pyogenesLinked to Severe Invasive Infections
Author:
Ono MasayukiORCID, Yamaguchi MasayaORCID, Motooka Daisuke, Hirose Yujiro, Higashi Kotaro, Sumitomo Tomoko, Miyoshi-Akiyama Tohru, Okuno Rumi, Yamaguchi Takahiro, Kawahara RyujiORCID, Otsuka Hitoshi, Nakanishi Noriko, Kazawa Yu, Nakagawa Chikara, Yamaguchi Ryo, Sakai Hiroo, Matsumoto Yuko, Ikebe TadayoshiORCID, Kawabata Shigetada
Abstract
SummaryStreptococcus pyogenescauses 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 ofemm89S. pyogenesstrains 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,fhuBT218C, 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 convertemm89S. pyogenesto an invasive phenotype and a platform for establishing novel treatments and prevention strategies.
Publisher
Cold Spring Harbor Laboratory
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