Biozentrum, University of Basel, Basel, Switzerland.
Institute of Microbiology, ETH Zurich, Zürich, Switzerland.
Nat Microbiol. 2021 Jan;6(1):59-72. doi: 10.1038/s41564-020-00809-4. Epub 2020 Nov 9.
Bacteria use small signalling molecules such as (p)ppGpp or c-di-GMP to tune their physiology in response to environmental changes. It remains unclear whether these regulatory networks operate independently or whether they interact to optimize bacterial growth and survival. We report that (p)ppGpp and c-di-GMP reciprocally regulate the growth of Caulobacter crescentus by converging on a single small-molecule-binding protein, SmbA. While c-di-GMP binding inhibits SmbA, (p)ppGpp competes for the same binding site to sustain SmbA activity. We demonstrate that (p)ppGpp specifically promotes Caulobacter growth on glucose, whereas c-di-GMP inhibits glucose consumption. We find that SmbA contributes to this metabolic switch and promotes growth on glucose by quenching the associated redox stress. The identification of an effector protein that acts as a central regulatory hub for two global second messengers opens up future studies on specific crosstalk between small-molecule-based regulatory networks.
细菌使用小分子信号分子（如（p）ppGpp 或 c-di-GMP）来响应环境变化调整其生理机能。目前尚不清楚这些调控网络是独立运作的，还是相互作用以优化细菌的生长和存活。我们报告说，（p）ppGpp 和 c-di-GMP 通过汇聚到单个小分子结合蛋白 SmbA 来相互调节新月柄杆菌的生长。虽然 c-di-GMP 结合抑制 SmbA，但（p）ppGpp 竞争相同的结合位点以维持 SmbA 的活性。我们证明（p）ppGpp 特异性促进新月柄杆菌在葡萄糖上的生长，而 c-di-GMP 抑制葡萄糖的消耗。我们发现 SmbA 有助于这种代谢转换，并通过缓解相关的氧化还原应激来促进葡萄糖生长。鉴定出一种效应蛋白，它作为两种全局第二信使的中央调控枢纽，为基于小分子的调控网络之间的特定串扰的未来研究开辟了道路。
