Reciprocal growth control by competitive binding of nucleotide second messengers to a metabolic switch in Caulobacter crescentus

ABSTRACT: Bacteria use a range of small signaling molecules to tune their physiology in response to changes in the environment. It has remained unclear if these regulatory networks operate independently or if they interact to optimize bacterial growth and survival. Here, we demonstrate that (p)ppGpp and c-di-GMP reciprocally regulate growth of Caulobacter crescentus by converging on a single small-molecule-binding protein, SmbA. Both second messengers bind to SmbA with high affinity and in a competitive manner, with the guanine moiety of (p)ppGpp and one of the guanyl bases of dimeric c-di-GMP forming identical interactions with SmbA. While c-di-GMP binding inhibits SmbA, (p)ppGpp interferes with this inhibition to sustain SmbA activity. We demonstrate that (p)ppGpp specifically promotes Caulobacter growth on glucose, while c-di-GMP inhibits glucose consumption. We find that SmbA contributes to this metabolic switch and promotes growth on glucose by quenching redox stress under these conditions. The identification of the first effector protein that acts as a central regulatory hub for two global second messengers opens up future studies on specific cross-talk between small-molecule-based regulatory networks.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Caulobacter Crescentus (strain Na1000 / Cb15n)

SUBMITTER: Thomas Bock  

LAB HEAD: Alexander Schmidt

PROVIDER: PXD019846 | Pride | 2020-12-08

REPOSITORIES: Pride