Autoinducer-2 and bile salts induce c-di-GMP synthesis to repress the T3SS via a T3SS chaperone

• Published in: Nature communications 2022-11, Vol.13 (1), p.6684-6684, Article 6684
• Main Authors: Li, Shuyu, Sun, Hengxi, Li, Jianghan, Zhao, Yujiao, Wang, Ruiying, Xu, Lei, Duan, Chongyi, Li, Jialin, Wang, Zhuo, Liu, Qinmeng, Wang, Yao, Ouyang, Songying, Shen, Xihui, Zhang, Lei
• Format: Article
• Language: English
• Subjects: 13/1; 13/95; 14/5; 38/39; 38/88; 38/90; 42/41; 45/70; 631/326/41/2531; 631/326/41/2533; 631/326/421; 64/60; 82/58; 82/80; 82/83; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bile Acids and Salts; Bile salts; Biofilms; Biological activity; Cell signaling; Cyclic GMP - metabolism; Domains; Effectors; Environmental effects; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene expression; Gene Expression Regulation, Bacterial; Humanities and Social Sciences; Intracellular; Metabolism; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; multidisciplinary; Population density; Quorum sensing; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Salts; Science; Science (multidisciplinary); Stimuli; Synthesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34607-9

Cyclic di-GMP (c-di-GMP) transduces extracellular stimuli into intracellular responses, coordinating a plethora of important biological processes. Low levels of c-di-GMP are often associated with highly virulent behavior that depends on the type III secretion system (T3SS) effectors encoded, whereas elevated levels of c-di-GMP lead to the repression of T3SSs. However, extracellular signals that modulate c-di-GMP metabolism to control T3SSs and c-di-GMP effectors that relay environmental stimuli to changes in T3SS activity remain largely obscure. Here, we show that the quorum sensing signal autoinducer-2 (AI-2) induces c-di-GMP synthesis via a GAPES1 domain-containing diguanylate cyclase (DGC) YeaJ to repress T3SS-1 gene expression in Salmonella enterica serovar Typhimurium. YeaJ homologs capable of sensing AI-2 are present in many other species belonging to Enterobacterales . We also reveal that taurocholate and taurodeoxycholate bind to the sensory domain of the DGC YedQ to induce intracellular accumulation of c-di-GMP, thus repressing the expression of T3SS-1 genes. Further, we find that c-di-GMP negatively controls the function of T3SSs through binding to the widely conserved CesD/SycD/LcrH family of T3SS chaperones. Our results support a model in which bacteria sense changes in population density and host-derived cues to regulate c-di-GMP synthesis, thereby modulating the activity of T3SSs via a c-di-GMP-responsive T3SS chaperone. Cyclic-di-GMP transduces extracellular stimuli into intracellular responses to modulate important biological processes. Here, the authors show that AI-2 and bile salts induce cyclic-di-GMP synthesis via YeaJ and YedQ, respectively, to repress the T3SS via a cyclic-di-GMP-responsive T3SS chaperone.