Elucidation of function of increasing toxin in the streptococcal toxic shock syndrome clinical isolates and of the regulation

链球菌中毒性休克综合征（STSS）是一种严重的侵袭性感染，其特征是突然发生休克和多器官功能衰竭;它具有很高的死亡率。在本研究中，另一个负调节基因rgg的突变也在STSS患者的临床分离株中发现。来自STSS临床分离株的rgg突变体增强了小鼠模型中的致死性并损害了各种器官，并阻止了它们被人中性粒细胞杀死。在检测沙门氏菌rgg基因突变频率时，从STSS和非侵袭性感染的化脓性链球菌分离株中，约25%的STSS分离株具有rgg基因突变，而来自非侵袭性疾病患者的分离株具有显著较少的该基因突变（1.7%）。本研究结果提示，S.化脓性链球菌是STSS发病机制中的关键因素，因为它们导致多种毒力因子的过度产生。

Streptococcal toxic shock syndrome(STSS) is a severe invasive infection characterized by the sudden onset of shock and multiorgan failure ; it has a high mortality rate. In the present study, mutations of another negative regulator, rgg, were also found in clinical isolates of STSS patients. The rgg mutants from STSS clinical isolates enhanced lethality and impaired various organs in the mouse models and precluded their being killed by human neutrophils. When we assessed the mutation frequency of rgg gene among S. pyogenes isolates from STSS and non-invasive infections, about 25% of the STSS isolates had mutations of rgg gene, while isolates from patients with non-invasive disease had significantly fewer mutations in this gene(1.7%). The results of the present study suggest that mutations in the negative regulators csrS/csrR and rgg of S. pyogenes are crucial factors in the pathogenesis of STSS, as they lead to the overproduction of multiple virulence factors.