Pathobionts associated with periodontitis, such as Treponema denticola, must possess numerous sensory transduction systems to adapt to the highly dynamic subgingival environment. To date, the signaling pathways utilized by T. denticola to rapidly sense and respond to environmental stimuli are mainly unknown. Bis‐(3′–5′) cyclic diadenosine monophosphate (c‐di‐AMP) is a nucleotide secondary messenger that regulates osmolyte transport, central metabolism, biofilm development, and pathogenicity in many bacteria but is uncharacterized in T. denticola. Here, we studied c‐di‐AMP signaling in T. denticola to understand how it contributes to T. denticola physiology. We demonstrated that T. denticola produces c‐di‐AMP and identified enzymes that function in the synthesis (TDE1909) and hydrolysis (TDE0027) of c‐di‐AMP. To investigate how c‐di‐AMP may impact T. denticola cellular processes, a screening assay was performed to identify putative c‐di‐AMP receptor proteins. This approach identified TDE0087, annotated as a potassium uptake protein, as the first T. denticola c‐di‐AMP binding protein. As potassium homeostasis is critical for maintaining turgor pressure, we demonstrated that T. denticola c‐di‐AMP concentrations are impacted by osmolarity, suggesting that c‐di‐AMP negatively regulates potassium uptake in hypoosmotic solutions. Collectively, this study demonstrates T. denticola utilizes c‐di‐AMP signaling, identifies c‐di‐AMP metabolism proteins, identifies putative receptor proteins, and correlates c‐di‐AMP signaling to osmoregulation.

中文翻译：

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牙周病菌（齿垢密螺旋体）中 c-di-AMP 信号传导的特征

与牙周炎相关的病原体，例如齿螺旋体，必须拥有众多的感觉传导系统以适应高度动态的龈下环境。迄今为止，所利用的信号通路齿毛毛虫快速感知和响应环境刺激的能力主要还是未知的。双-(3′–5′)环二腺苷单磷酸 (c-di-AMP) 是一种核苷酸第二信使，可调节许多细菌中的渗透剂运输、中枢代谢、生物膜发育和致病性，但在许多细菌中尚未被表征。齿毛毛虫。在这里，我们研究了 c-di-AMP 信号传导齿毛毛虫了解它如何有助于齿毛毛虫生理。我们证明了齿毛毛虫产生 c-di-AMP 并鉴定出在 c-di-AMP 合成 (TDE1909) 和水解 (TDE0027) 中起作用的酶。研究 c-di-AMP 如何影响齿毛毛虫细胞过程中，进行了筛选测定来鉴定假定的 c-di-AMP 受体蛋白。该方法将 TDE0087（注释为钾摄取蛋白）确定为第一个齿毛毛虫c-di-AMP 结合蛋白。由于钾稳态对于维持膨胀压至关重要，我们证明了齿毛毛虫c-di-AMP 浓度受渗透压影响，表明 c-di-AMP 负向调节低渗溶液中钾的吸收。总的来说，这项研究表明齿毛毛虫利用 c-di-AMP 信号传导，识别 c-di-AMP 代谢蛋白，识别假定的受体蛋白，并将 c-di-AMP 信号传导与渗透压调节相关联。