Two-component systems (TCSs) are vital signal transduction pathways ubiquitous among bacteria, facilitating their responses to diverse environmental stimuli. In Bacillus subtilis, the DesK histidine kinase thermosensor, together with the response regulator DesR, constitute a TCS dedicated to membrane lipid homeostasis maintenance. This TCS orchestrates the transcriptional regulation of the des gene, encoding the sole desaturase in these bacteria, Δ5-Des. Additionally, B. subtilis possesses a paralog TCS, YvfT/YvfU, with unknown target gene(s). In this work, we show that YvfT/YvfU controls the expression of the yvfRS operon that codes for an ABC transporter. Interestingly, we found that this regulation also involves the action of DesK/DesR. Notably, opposite to des, yvfRS transcription is induced at 37°C and not at 25°C. Our in vivo and in vitro experiments demonstrate that both YvfU and DesR directly bind to the operon promoter region, with DesR exerting its control over yvfRS expression in its unphosphorylated state. Our study uncovers an intriguing case of cross-regulation where two homologous TCSs interact closely to finely tune gene expression in response to environmental cues. These findings shed light on the complexity of bacterial signal transduction systems and their critical role in bacterial adaptability.

中文翻译：

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揭示了 DesK/DesR 和 YvfT/YvfU 控制枯草芽孢杆菌中 ABC 转运蛋白表达的协同作用


双组分系统 （TCS） 是细菌中普遍存在的重要信号转导途径，可促进它们对各种环境刺激的反应。在枯草芽孢杆菌中，DesK 组氨酸激酶温度传感器与反应调节因子 DesR 一起构成了专用于维持膜脂质稳态的 TCS。该 TCS 协调 des 基因的转录调控，编码这些细菌中唯一的去饱和酶 Δ5-Des。此外，枯草芽孢杆菌具有一个旁系同源 TCS，即 YvfT/YvfU，靶基因未知。在这项工作中，我们表明 YvfT/YvfU 控制编码 ABC 转运蛋白的 yvfRS 操纵子的表达。有趣的是，我们发现这个调节还涉及 DesK/DesR 的作用。值得注意的是，与 des 相反，yvfRS 转录是在 37°C 而不是 25°C 下诱导的。 我们的体内和体外实验表明，YvfU 和 DesR 都直接与操纵子启动子区域结合，DesR 在未磷酸化状态下对 yvfRS 表达施加控制。我们的研究揭示了一个有趣的交叉调控案例，其中两个同源 TCS 紧密相互作用以响应环境线索微调基因表达。这些发现揭示了细菌信号转导系统的复杂性及其在细菌适应性中的关键作用。