Conjugative transfer of the integrative and conjugative element ICEclc in Pseudomonas requires development of a transfer competence state in stationary phase, which arises only in 3-5% of individual cells. The mechanisms controlling this bistable switch between non active and transfer competent cells have long remained enigmatic. Using a variety of genetic tools and epistasis experiments in P. putida, we uncovered an ‘upstream’ cascade of three consecutive transcription factor-nodes, which controls transfer competence initiation. Initiation activates a feedback loop, which stochastic modeling and experimental data demonstrated acts as a scalable converter of unimodal input to bistable output. The feedback loop further enables prolonged production of a transcription factor that ensures 'downstream' transfer competence formation in activated cells. Phylogenetic analyses showed that the ICEclc regulatory factors are widespread among Gamma- and Beta-proteobacteria, highlighting its evolutionary conservation and prime importance to control the behaviour of this wide family of conjugative elements.

中文翻译：

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模数转换器控制广泛的集成和共轭元件的双稳态传输能力

假单胞菌中整合和共轭元件ICEclc的共轭转移需要在固定相中发展转移能力状态，这种状态仅出现在3％至5％的单个细胞中。控制这种非稳态细胞和转移感受态细胞之间的双稳态转换的机制长期以来一直是个谜。使用恶臭假单胞菌中的多种遗传工具和上位性实验，我们发现了三个连续的转录因子节点的“上游”级联，该节点控制转移能力的启动。初始化激活了一个反馈回路，该回路证明了随机建模和实验数据可作为单峰输入到双稳态输出的可伸缩转换器。反馈回路还可以延长转录因子的产生，从而确保“下游” 在活化细胞中转移能力形成。系统发育分析表明，ICEclc调节因子在γ-和β-变形杆菌中广泛存在，突出了其进化保守性，并且对于控制这种广泛的结合元件家族的行为至关重要。