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.

细菌使用小信号分子，如 (p)ppGpp 或 c-di-GMP 来调整其生理学以响应环境变化。目前尚不清楚这些监管网络是否独立运作，或者它们是否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通过收敛于单个小分子结合蛋白 SmbA 来相互调节新月茎杆菌的生长。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 活性。我们证明 (p)ppGpp 专门促进Caulobacter葡萄糖的生长，而 c-di-GMP 抑制葡萄糖消耗。我们发现 SmbA 有助于这种代谢转换，并通过抑制相关的氧化还原应激来促进葡萄糖的生长。作为两个全球第二信使的中央调节中心的效应蛋白的鉴定为基于小分子的调节网络之间的特定串扰开辟了未来的研究。