Patino Ramiro, Kühn Marco J, Macmillan Henriette, Inclan Yuki F, Chavez Ivan, Von Dollen John, Johnson Jeffrey R, Swaney Danielle L, Krogan Nevan J, Persat Alexandre, Engel Joanne N
bioRxiv. 2024 Feb 27:2024.02.27.582188. doi: 10.1101/2024.02.27.582188.
Sensory signaling pathways use adaptation to dynamically respond to changes in their environment. Here, we report the mechanism of sensory adaptation in the Pil-Chp mechanosensory system, which the important human pathogen uses to sense mechanical stimuli during surface exploration. Using biochemistry, genetics, and cell biology, we discovered that the enzymes responsible for adaptation, a methyltransferase and a methylesterase, are segregated to opposing cell poles as explore surfaces. By coordinating the localization of both enzymes, we found that the Pil-Chp response regulators influence local receptor methylation, the molecular basis of bacterial sensory adaptation. We propose a model in which adaptation during mechanosensing spatially resets local receptor methylation, and thus Pil-Chp signaling, to modulate the pathway outputs, which are involved in virulence. Despite decades of bacterial sensory adaptation studies, our work has uncovered an unrecognized mechanism that bacteria use to achieve adaptation to sensory stimuli.
感觉信号通路利用适应性来动态响应其环境变化。在此,我们报告了Pil-Chp机械感觉系统中的感觉适应机制,这种重要的人类病原体在表面探索过程中利用该系统来感知机械刺激。通过生物化学、遗传学和细胞生物学方法,我们发现负责适应的酶,一种甲基转移酶和一种甲基酯酶,在细菌探索表面时被分隔到相对的细胞极。通过协调这两种酶的定位,我们发现Pil-Chp反应调节因子影响局部受体甲基化,这是细菌感觉适应的分子基础。我们提出了一个模型,其中机械传感过程中的适应在空间上重置局部受体甲基化,从而重置Pil-Chp信号传导,以调节与毒力相关的通路输出。尽管对细菌感觉适应的研究已有数十年,但我们的工作揭示了一种细菌用于实现对感觉刺激适应的未被认识的机制。