Bacterial c-di-GMP triggers metamorphosis of mussel larvae through a STING receptor

Abstract Bacteria induced metamorphosis observed in nearly all marine invertebrates. However, the mechanism of bacteria regulating the larvae-juvenile metamorphosis remains unknown. Here, we test the hypothesis that c-di-GMP, a ubiquitous bacterial second-messenger molecule, directly triggers the mollusc Mytilus coruscus larval metamorphosis via the stimulator of interferon genes (STING) receptor. We determined that the deletion of c-di-GMP synthesis genes resulted in reduced c-di-GMP levels and biofilm-inducing activity on larval metamorphosis, accompanied by alterations in extracellular polymeric substances. Additionally, c-di-GMP extracted from tested varying marine bacteria all exhibited inducing activity on larval metamorphosis. Simultaneously, through pharmacological and molecular experiments, we demonstrated that M. coruscus STING ( Mc STING) participates in larval metamorphosis by binding with c-di-GMP. Our findings reveal that new role of bacterial c-di-GMP that triggers mussel larval metamorphosis transition, and extend knowledge in the interaction of bacteria and host development in marine ecosystems.