Searching for environmental signals sensed by group A streptococcal two-component systems

化脓性链球菌（Streptococcus pyogenes）（A组链球菌; GAS）是引起多种疾病的人类病原体，所述疾病的范围从自限性化脓性感染（例如咽炎、扁桃体炎和脓疱病）到严重坏死性筋膜炎和自身免疫性疾病（包括急性风湿热和肾小球肾炎）。为了成功逃避宿主的免疫反应并引起多种疾病，GAS可能适应环境变化并控制包括毒力基因在内的多种基因的表达。在这项研究中，编码组氨酸激酶和反应调节因子的基因的缺失突变体的背景下构建的血清型M3 GAS株。利用这些突变株和家蚕感染模型，我们发现，几个双组分系统是至关重要的GAS发病机制。此外，在几种培养条件下的突变株的毒力基因表达的分析表明，特定的环境信号的双组分系统。

Streptococcus pyogenes (group A streptococci; GAS) is a human pathogen responsible for a wide variety of diseases that ranges from self-limiting purulent infections such as pharyngitis, tonsillitis, and impetigo to severe necrotizing fasciitis and autoimmune diseases including acute rheumatic fever and glomerulonephritis. To successfully evade host immune responses and cause such diverse diseases, GAS might acclimate to environmental changes and control the expression of a variety of genes including virulence genes. In this study, deletion mutants of genes encoding both histidine kinases and response regulators were constructed in a background of a serotype M3 GAS strain. Utilizing these mutant strains and a silkworm infection model, we revealed that several two-component systems are crucial for GAS pathogenesis. Moreover, analysis of the virulence gene expression in mutant strains under several culture conditions indicated specific environmental signals are sensed by two-component systems.