Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence.
Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence.
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DOI：
10.1038/srep28761
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发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Ohnishi M
中科院分区：
文献类型：
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作者：
Ikebe T;Matsumura T;Nihonmatsu H;Ohya H;Okuno R;Mitsui C;Kawahara R;Kameyama M;Sasaki M;Shimada N;Ato M;Ohnishi M
化脓性链球菌（Streptococcus pyogenes，A组链球菌; GAS）是一种广泛分布的人类病原体，并引起链球菌中毒性休克综合征（STSS）。先前已显示STSS分离株在csrS/csrR（covS/covR）和/或rgg（ropB）基因中具有高频率突变，这是毒力的负调节因子。然而，这些突变被发现在emm 1基因型分离株，最流行的STSS基因型的频率有点低。在这项研究中，我们试图检测缺乏csrS/csrR和rgg基因突变的emm 1分离株中增强毒力的因果突变。在sic（毒力基因）启动子、csrR启动子和rocA基因（csrR正调控基因）中发现了三个与毒力升高相关的突变。在GAS小鼠模型中证实了sic启动子和rocA突变对致病性和致死性的体内贡献。sic启动子突变的频率显着高于在STSS emm 1分离株比非侵袭性STSS分离株; rocA基因突变的频率之间没有显着差异STSS和非STSS分离株。STSS emm 1菌株在sic启动子中具有高频率突变。因此，这种突变可能在毒力动力学和STSS发病机制中发挥作用。
Streptococcus pyogenes (group A Streptococcus; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the csrS/csrR (covS/covR) and/or rgg (ropB) genes, which are negative regulators of virulence. However, these mutations were found at somewhat low frequencies in emm1-genotyped isolates, the most prevalent STSS genotype. In this study, we sought to detect causal mutations of enhanced virulence in emm1 isolates lacking mutation(s) in the csrS/csrR and rgg genes. Three mutations associated with elevated virulence were found in the sic (a virulence gene) promoter, the csrR promoter, and the rocA gene (a csrR positive regulator). In vivo contribution of the sic promoter and rocA mutations to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the sic promoter mutation was significantly higher in STSS emm1 isolates than in non-invasive STSS isolates; the rocA gene mutation frequency was not significantly different among STSS and non-STSS isolates. STSS emm1 isolates possessed a high frequency mutation in the sic promoter. Thus, this mutation may play a role in the dynamics of virulence and STSS pathogenesis.