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)是一种以突发性休克和多器官衰竭为特征的严重侵袭性感染，病死率高。在本研究中，在STSS患者的临床分离株中也发现了另一种负调控因子RGG的突变。STSS临床分离株的RGG突变体提高了小鼠模型的致死率，损害了小鼠的各种器官，并阻止了它们被人中性粒细胞杀死。当我们评估STSS和非侵袭性感染的化脓性链球菌中RGG基因的突变频率时，大约25%的STSS分离株存在RGG基因突变，而来自非侵袭性疾病的分离株的RGG基因突变明显较少(1.7%)。本研究结果提示，化脓性链球菌的负调控基因CSRS/csrR和RgG的突变是STSS致病的关键因素，因为它们导致多种毒力因子的过量产生。

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.