A群鏈球菌是人類主要致病菌之一，受其感染後會產生多樣之症狀，從輕微感染到致死性疾病都有機會發生。目前已知A群鏈球菌以嚴謹的調控系統促使在in vitro培養下不同基因會於特定時間點表現。如A群鏈球菌的主要毒力因子，鏈球菌熱源性外毒素B (SpeB)，僅表現於stationary phase。在本研究中，我們發現透過添加隔夜培養液，可以誘發A群鏈球菌於log phase表現speB；這顯示A群鏈球菌的speB時態調控 (temporal regulation) 是透過不同時間點的培養液成分差異而達成的。而在隔夜培養液含有的眾多訊息中，葡萄糖不足與培養液酸化可以正向調控speB之表現，但由LuxS與peptide AI-1所調控的群體密度調控系統則不能影響speB的表現。透過proteinase K的處理，本研究也發現A群鏈球菌的膜蛋白質對於speB之表現有關連。利用生物資訊學的分析以及比較基因表現之差異，本研究發現speB的正向調控因子，Rgg，在受隔夜培養液刺激後，表現量也會上升。此外，若於early log phase提升rgg的表現量也可直接引起speB表現，而這現象在具有Rgg調控功能抑制基因，lacD.1，存在的A群鏈球菌中也被發現。綜合前述，本研究推論speB的時態調控系統是藉由不同時態的培養液刺激來掌握，而A群鏈球菌也會利用Rgg統合來自於隔夜培養液的各式刺激，進而開啟speB之表現。

Group A streptococcus (GAS) is one of the major human pathogens, and it can cause versatile diseases, from self-limited to life-threatening diseases. Gene expression in GAS is tightly controlled in a temporal manner in vitro. Here we showed that streptococcal pyrogenic exotoxin B (speB), which normally expresses in stationary phase, can be induced in log phase under overnight-cultured medium stimulation. It indicates that temporal regulation of speB is dependent on medium composition. Acid and glucose starvation in overnight-cultured medium can contribute speB expression, while LuxS-mediated and peptide AI-1-mediated quorum sensing can not. By proteinase K treatment, we also found that membrane proteins on GAS can also contribute to speB expression. Combining bioinformatic approaches and gene expression analysis, we found that Rgg, the positive regulator of speB, can be induced under overnight-cultured medium stimulation. Over expression of rgg in early log phase can directly lead to speB expression even in the strain with the lacD.1, which can go through protein interaction to trap Rgg and to prevent speB expression in log phase. Thus temporal regulation of speB in GAS can be accomplished by differential environmental stimulation and Rgg can coordinate all input signals to turn on speB expression.

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